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SEVENTH EDITION
VOLUME 1

Irwin and Rippes


INTENSIVE CARE
MEDICINE

Editors
Richard S. Irwin, MD, James M. Rippe, MD
Master FCCP Professor of Biomedical Sciences, University of
Professor of Medicine and Nursing Central Florida
University of Massachusetts Orlando, Florida
Worcester, Massachusetts Associate Professor of Medicine (Cardiology),
Chair, Critical Care Operations Tufts University School of Medicine
UMass Memorial Medical Center Boston, Massachusetts
Worcester, Massachusetts Founder and Director, Rippe Lifestyle Institute
Shrewsbury, Massachusetts
Founder and Director, Rippe Health Evaluation
Orlando, Florida

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Acquisitions Editor: Brian Brown


Managing Editor: Nicole T. Dernoski
Marketing Manager: Angela Panetta
Production Manager: Alicia Jackson
Senior Manufacturing Manager: Benjamin Rivera
Design Coordinator: Teresa Mallon
Compositor: Aptara, Inc.

7th Edition
2012 by Richard S. Irwin, M.D. and James M. Rippe, M.D.
530 Walnut Street
Philadelphia, PA 19106
LWW.com

6th Edition 2008 by Richard S. Irwin, M.D. and James M. Rippe, M.D., 5th Edition 2003 by
Richard S. Irwin, M.D. and James M. Rippe, M.D., 4th Edition 1999 by Richard S. Irwin, M.D.,
Frank B. Cerra, M.D., and James M. Rippe, M.D., 3rd Edition 1996 by James M. Rippe, M.D.,
Richard S. Irwin, M.D., Mitchell P. Fink, M.D., and Frank B. Cerra, M.D., 2nd Edition 1991 by
James M. Rippe, M.D., Richard S. Irwin, M.D., Joseph S. Alpert, M.D., and Mitchell P. Fink, M.D.,
1st Edition 1985 by James M. Rippe, M.D., Richard S. Irwin, M.D., Joseph S. Alpert, M.D., and
James E. Dalen, M.D.

All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any
form or by any means, including photocopying, or utilized by any information storage and retrieval
system without written permission from the publisher, except for brief quotations embodied in critical
articles and reviews. For information write Lippincott Williams & Wilkins, 530 Walnut Street,
Philadelphia, PA 19106-3780.

Materials appearing in this book prepared by individuals as part of their official duties as U.S.
government employees are not covered by the above-mentioned copyright.

Printed in the China

Library of Congress Cataloging-in-Publication Data

Irwin and Rippes intensive care medicine / editors, Richard S. Irwin,


James M. Rippe. 7th ed.
p. ; cm.
Intensive care medicine
Includes bibliographical references and index.
ISBN 978-1-60831-183-5 (alk. paper)
1. Critical care medicine. I. Irwin, Richard S. II. Rippe, James M.
III. Title: Intensive care medicine.
[DNLM: 1. Intensive Caremethods. 2. Intensive Care Units. WX 218]
RC86.7.I555 2011
616.02 8dc23
2011021282

Care has been taken to confirm the accuracy of the information presented and to describe generally
accepted practices. However, the authors, editors, and publisher are not responsible for errors or
omissions or for any consequences from application of the information in this book and make no
warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents
of the publication. Application of this information in a particular situation remains the professional
responsibility of the practitioner.
The authors, editors, and publisher have exerted every effort to ensure that drug selection and
dosage set forth in this text are in accordance with current recommendations and practice at the time of
publication. However, in view of ongoing research, changes in government regulations, and the constant
flow of information relating to drug therapy and drug reactions, the reader is urged to check the package
insert for each drug for any change in indications and dosage and for added warnings and precautions.
This is particularly important when the recommended agent is a new or infrequently employed drug.
Some drugs and medical devices presented in this publication have Food and Drug Administration
(FDA) clearance for limited use in restricted research settings. It is the responsibility of the health care
provider to ascertain the FDA status of each drug or device planned for use in their clinical practice.

To purchase additional copies of this book, call our customer service department at (800) 638-3030 or
fax orders to (301) 223-2320. International customers should call (301) 223-2300.

Visit Lippincott Williams & Wilkins on the Internet: at LWW.com. Lippincott Williams & Wilkins
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D E D I C AT I O N

To Our Families

Diane, Rachel, Sara, Catherine, Rebecca, John, Andrew K. Andrew M. and Adam;
Stephanie, Hart, Jaelin, Devon, and Jamie

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CONTRIBUTORS

Cynthia K. Aaron, MD, FACMT, FACEP Satya Allaparthi, MD


Professor of Emergency Medicine and Pediatrics Fellow in Robotic and Laparoscopic Urology
Program Director, Medical Toxicology Department of Urology/Surgery
Department of Emergency Medicine UMass Memorial Medical Center
Wayne State University School of Medicine Worcester, MA
Detroit Medical Center
Regional Poison Center at Childrens Hospital of Michigan Gilman B. Allen, MD
Detroit, MI Assistant Professor
Director, Medical Intensive Care Unit
Wissam Abouzgheib, MD, FCCP Department of Medicine
Attending Physician Division of Pulmonary and Critical Care Medicine
Department of Pulmonary and Critical Care University of Vermont
Sparks Health System Fletcher Allen Health Care
Fort Smith, AR Burlington, VT

Gregory A. Abrahamian, MD Luis F. Angel, MD


Associate Professor of Surgery Associate Professor of Medicine
Department of Surgery Department of Medicine
University of Texas Health Science Center at San Antonio University of Texas Health Sciences Center at San Antonio
San Antonio, TX San Antonio, TX

Konstantin Abramov, MD Kevin E. Anger, PharmD, BCPS


Assistant Professor of Medicine Clinical Pharmacy Specialist in Critical Care
Division of Renal Medicine Department of Pharmacy Services
UMass Memorial Medical Center Brigham and Womens Hospital
Worcester, MA Boston, MA

Christopher D. Adams, PharmD, BCPS Derek C. Angus, MD, MPH


Clinical Pharmacist Professor and Vice Chair for Research
Department of Pharmacy Services Department of Critical Care Medicine
Brigham and Womens Hospital University of Pittsburgh Medical Center
Boston, MA Pittsburgh, PA

Suresh Agarwal, MD, FACS, FCCM Neil Aronin, MD


Chief, Surgical Critical Care Professor of Medicine and Cell Biology
Associate Professor of Surgery Chief of Endocrinology and Metabolism
Boston Medical Center Department of Medicine
Boston, MA University of Massachusetts Medical School
Worcester, MA
Lauren Alberta-Wszolek, MD
Assistant Professor of Medicine Samuel J. Asirvatham, MD, FACC, FHRS
Division of Dermatology Professor of Medicine and Pediatrics
University of Massachusetts Medical School Division of Cardiovascular Diseases
Worcester, MA Mayo Clinic College of Medicine
Rochester, MN
Alfred Aleguas Jr, PharmD, DABAT
Managing Director Seth M. Arum, MD, FACE
Northern Ohio Poison Center Assistant Professor of Medicine
Rainbow Babies & Childrens Hospital Department of Endocrinology
Cleveland, OH UMass Memorial Medical Center
Worcester, MA

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vi Contributors

Philip J. Ayvazian, MD Stephen L. Barnes, MD, FACS


Assistant Professor Associate Professor and Chief, Division of Acute
Department of Urology Care Surgery
UMass Memorial Medical Center Department of Surgery
Worcester, MA University of Missouri
Columbia, MO
Riad Azar, MD
Associate Professor of Medicine Suzanne J. Baron, MD
Department of Internal Medicine Cardiology Fellow
Division of Gastroenterology Department of Cardiology
Washington University School of Medicine Massachusetts General Hospital
Barnes Jewish Hospital Boston, MA
St. Louis, MO
Thaddeus C. Bartter, MD, FCCP
Ruben J. Azocar, MD Professor of Medicine
Associate Professor and Residency Program Director Department of Medicine
Department of Anesthesiology Division of Pulmonary and Critical Care
Boston University Medical Center University of Arkansas for the Medical Sciences
Boston, MA Little Rock, AR

Ednan K. Bajwa, MD, MPH Amit Basu, MD


Associate Director, Medical ICU Assistant Professor of Surgery and Attending Physician
Department of Pulmonary and Critical Care Department of Surgery
Massachusetts General Hospital University of Pittsburgh Medical Center
Boston, MA Thomas E Starzl Transplantation Institute
Pittsburgh, PA
K.C. Balaji, MD
Professor, Department of Surgery Kenneth L. Baughman, MD (DECEASED)
Division of Urology
UMass Memorial Medical Center
Worcester, MA Richard C. Becker, MD
Professor of Medicine
Jerry P. Balikian, MD, FACR Department of Medicine
Professor and Vice Chair of Radiology Duke University School of Medicine
Department of Radiology Durham, NC
University of Massachusetts Medical School
Worcester, MA Robert W. Belknap, MD
Assistant Professor of Medicine
Ian M. Ball, MD, DABEM, FRCPC Division of Infectious Diseases
Assistant Professor Denver Health and Hospital Authority
Program in Critical Care Medicine and University of Colorado
Departments of Clinical Pharmacology/Toxicology Denver, CO
and Emergency Medicine
Queens University Kingston Isabelita R. Bella, MD
Ontario, Canada Associate Professor of Clinical Neurology
Department of Neurology
Meyer S. Balter, MD, FRCPC University of Massachusetts Medical School
UMass Memorial Medical Center
Professor
Worcester, MA
Department of Medicine
University of Toronto
Director, Asthma Education Clinic
Andrew C. Bernard, MD
Mount Sinai Hospital Associate Professor of Surgery
Toronto, Ontario, Canada Department of Surgery
University of Kentucky Healthcare
Lexington, KY
Gisela I. Banauch, MD, MS
Assistant Professor of Medicine Division of Pulmonary, Megan Bernstein, MD
Allergy, Critical Care and Sleep Medicine Resident
University of Massachusetts Medical School Department of Dermatology
UMass Memorial Medical Center University of Massachusetts Medical School
Worcester, MA Worcester, MA

Daniel T. Baran, MD Mary T. Bessesen, MD


Region Medical Director Associate Professor of Medicine
Merck Department of Medicine
Adjunct Professor of Medicine, Cell Biology, and Orthopedics University of Colorado at Denver
UMass Memorial Medical Center Department of Veterans Affairs Medical CenterDenver
Worcester, MA Denver, CO
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Contributors vii

Michael C. Beuhler, MD Veronica Brito, MD


Medical Director Pulmonary and Critical Care Medicine Fellow
Department of Emergency Medicine Department of Medicine
Carolinas Poison Center Winthrop-University Hospital
Charlotte, NC Mineola, NY

Bonnie J. Bidinger, MD Traci L. Buescher, RN


Assistant Professor of Medicine Department of Heart Rhythm Services
Department of Internal Medicine Mayo Clinic
Division of Rheumatology Rochester, MN
University of Massachusetts Medical School
UMass Memorial Medical Center Keith K. Burkhart, MD, FACMT, FAACT, FACEP
Worcester, MA
Senior Advisor for Medical Toxicology
FDA Center for Drug Evaluation and Research
Steven B. Bird, MD Office of New Drugs
Associate Professor Silver Spring, MD
Department of Emergency Medicine
Division of Medical Toxicology
Michael J. Burns, MD, FACEP, FACMT
University of Massachusetts Medical School
Worcester, MA Chief of Emergency Medicine
Saint Vincent Hospital
Bruce R. Bistrian, MD, PhD Worcester, MA
Division of Medical Toxicology
Professor of Medicine
Department of Emergency Medicine
Harvard Medical School
Beth Israel Deaconess Medical Center
Department of Medicine
Boston, MA
Beth Israel Deaconess Medical Center
Boston, MA
Tuesday E. Burns, MD
Robert M. Black, MD Assistant Professor of Psychiatry
Professor of Clinical Medicine Department of Psychiatry
UMass Medical School Eastern Virginia Medical School
Chief, Nephrology Norfolk, VA
Division of Renal Medicine
St. Vincent Hospital Scott W. Byram, MD
Worcester, MA Assistant Professor of Anesthesiology
Department of Anesthesiology
Ernest F.J. Block, MD, MBA, FACS, FCCM Loyola University Medical Center
Professor of Surgery, University of Central Florida Maywood, IL
Department of Acute Care Surgery
Holmes Regional Medical Center Brian T. Callahan, MD
Melbourne, FL Interventional Radiology Fellow
Department of Radiology
Jeremiah Boles, MD Harvard Medical School
Hematology/Oncology Fellow Beth Israel Deaconess Medical Center
Department of Medicine Boston, MA
Division of Hematology/Oncology
University of North Carolina at Chapel Hill Christine Campbell-Reardon, MD
Chapel Hill, NC Associate Professor of Medicine
Department of Pulmonary and Critical Care
Naomi F. Botkin, MD Medicine
Assistant Professor of Medicine Boston University School of Medicine
Division of Cardiovascular Medicine Boston Medical Center
UMass Memorial Medical Center Boston, MA
Worcester, MA
Christopher P. Cannon, MD
Suzanne F. Bradley, MD TIMI Study Group
Professor Cardiovascular Division
Department of Internal Medicine Brigham and Womens Hospital
Division of Infectious Diseases and Geriatric Medicine Associate Professor of Medicine, Harvard
Veterans Affairs Ann Arbor Medical School
University of Michigan Healthcare Systems Boston, MA
Ann Arbor, MI
Jason P. Caplan, MD
William F. Bria, MD Chief of Psychiatry
Chief Medical Information Officer Department of Psychiatry
Department of Medical Affairs Creighton University School of Medicine at St. Josephs
Shriners Hospital for Children Hospital and Medical Center
Tampa, FL Phoenix, AZ
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viii Contributors

Raphael A. Carandang, MD Victor G. Cimino, MD, FACS


Assistant Professor Associate Professor
University of Massachusetts Medical School Department of Surgery
Department of Neurology and Surgical Intensive Care Loyola University Medical Center
UMass Memorial Medical Center Maywood, IL
Worcester, MA
Mary Dawn T. Co, MD
Paul A. Carpenter, MD Assistant Professor of Medicine
Associate Professor University of Massachusetts Medical School
Clinical Research Division UMass Memorial Medical Center
Fred Hutchinson Cancer Research Center Worcester, MA
Seattle, WA
Shawn Cody, MSN, MBA, RN
Karen C. Carroll, MD Associate Chief Nursing Officer for Critical Care
Professor Pathology and Medicine UMass Memorial Medical Center
Department of Pathology Worcester, MA
Division of Medical Microbiology
Johns Hopkins Hospital Felipe B. Collares, MD, MSc
Baltimore, MD Interventional Radiologist
Department of Radiology
David A. Chad, MD Beth Israel Deaconess Medical Center
Associate Professor of Neurology Instructor in Radiology
Harvard Medical School Harvard Medical School
Department of Neurology Boston, MA
Massachusetts General Hospital
Neuromuscular Diagnostic Center Bryan R. Collier, MD
Boston, MA Assistant Professor of Surgery
Division of Trauma & Surgical Critical Care
Eugene Chang, MD Vanderbilt University Medical Center
Martin Boyer Professor of Medicine Nashville, TN
Department of Medicine, Section of Gastroenterology
University of Chicago Nancy A. Collop, MD
Chicago, IL
Professor of Medicine
Steven Y. Chang, MD, PhD Department of Medicine
Emory University
Assistant Professor of Medicine
Atlanta, GA
Division of Pulmonary & Critical Care Medicine
Director of the Medical Intensive Care Unit
John B. Cone, MD, FACS, FCCM
University of Medicine & Dentistry of New Jersey
New Jersey Medical School Professor of Surgery
Newark, NJ Norma & Nolie Mumey Chair in General Surgery
Department of Surgery
Michael L. Cheatham, MD, FACS, FCCM University of Hospital of Arkansas
Director, Surgical Intensive Care Units Little Rock, AR
Department of Surgical Education
Orlando Regional Medical Center Sara E. Cosgrove, MD
Orlando, FL Associate Professor of Medicine
Division of Infectious Disease
Sarah H. Cheeseman, MD Johns Hopkins Medical Institutions
Professor of Medicine, Pediatrics, Microbiology and Baltimore, MD
Molecular Genetics
University of Massachusetts Medical School Filippo Cremonini, MD, PhD
Division of Infectious Diseases Attending Physician
UMass Memorial Medical Center Department of Gastroenterology
Worcester, MA Beth Israel Deaconess Medical Center
Harvard Medical School
Annabel A. Chen-Tournoux, MD Boston, MA
Cardiology Fellow
Department of Medicine Jonathan F. Critchlow, MD
Division of Cardiology Assistant Professor of Surgery
Massachusetts General Hospital Harvard University
Boston, MA Beth Israel Deaconess Medical Center
Boston, MA
William K. Chiang, MD
Chief of Service and Associate Professor of Emergency Ruy J. Cruz Jr, MD, PhD
Medicine Assistant Professor of Surgery
Department of Emergency Department of Surgery
Bellevue Hospital Center University of Pittsburgh Medical Center
New York, NY Pittsburgh, PA
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Contributors ix

Frederick J. Curley, MD Gregory J. Della Rocca, MD, PhD, FACS


Associate Professor of Medicine Assistant Professor
University of Massachusetts Medical School Co-Director, Orthopaedic Trauma Service
Lung, Allergy & Sleep Specialists Department of Orthopaedic Surgery
Hopedale, MA University of Missouri
Columbia, MO
Armagan Dagal, MD, FRCA
Assistant Professor Thomas G. DeLoughery, MD, FACP
Department of Anesthesiology and Pain Medicine Professor of Medicine, Pathology and Pediatrics
University of Washington, Harborview Medical Center Department of Hematology
Seattle, WA Oregon Health and Science University
Portland, OR
Seth T. Dahlberg, MD
Associate Professor of Medicine and Radiology Mario De Pinto, MD
Department of Medicine and Radiology Assistant Professor
University of Massachusetts Medical School Department of Anesthesiology
Division of Cardiology University of Washington
UMass Memorial Medical Center Harborview Medical Center
Worcester, MA Seattle, WA

Frank F. Daly, MBBS Mark Dershwitz, MD, PhD


Clinical Toxicologist and Emergency Physician Professor and Vice Chair of Anesthesiology
Department of Emergency Medicine Professor of Biochemistry & Molecular Pharmacology
Royal Perth Hospital UMass Memorial Medical Center
Western Australia, Australia Worcester, MA

Jennifer S. Daly, MD Akshay S. Desai, MD


Professor of Medicine Instructor in Medicine
Clinical Chief, Infectious Diseases and Immunology Harvard Medical School
Department of Medicine Associate Physician
University of Massachusetts Medical School Cardiovascular Division
Worcester, MA Department of Medicine
Brigham and Womens Hospital
Lloyd E. Damon, MD Boston, MA
Professor of Clinical Medicine
Department of Medicine Asha Devereaux, MD, MPH
University of California, San Francisco Pulmonary Physician
San Francisco, CA Sharp Coronado Hospital
Coronado, CA
Raul E. Davaro, MD
Associate Professor, Clinical Medicine Christopher R. DeWitt, MD
Department of Medicine Medical Toxicologist and Emergency Physician
University of Massachusetts Medical School Department of Emergency and British Columbia
Worcester, MA Poison Center
Saint Pauls Hospital
Wellington J. Davis III, MD University of British Columbia
Assistant Professor of Surgery and Pediatrics Vancouver, BC
Section of Plastic and Reconstructive Surgery
St. Christophers Hospital for Children Peter Doelken, MD
Philadelphia, PA
Associate Professor
Ronald J. DeBellis, PharmD, FCCP Department of Medicine
Division of Pulmonary, Critical Care, Allergy &
Professor and Chair
Sleep Medicine
Department of Pharmacy Practice
Medical University of South Carolina
Albany College of Pharmacy and Health SciencesVermont
Charleston, SC
Colchester, VT
G. William Dec, MD Robert P. Dowsett, FACEM
Chief, Cardiology Division Senior Staff Specialist
Massachusetts General Hospital Department of Emergency Medicine
Department of Cardiology Westmead Hospital
Boston, MA Wentworthville, NSW, Australia

Paul F. Dellaripa, MD David A. Drachman, MD


Assistant Professor of Medicine Professor of Neurology
Harvard Medical School Chairman Emeritus
Division of Rheumatology Department of Neurology
Brigham and Womens Hospital University of Massachusetts Medical School
Boston, MA Worcester, MA
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x Contributors

David F. Driscoll, PhD Timothy A. Emhoff, MD


Vice President Chief, Trauma, Surgical Critical Care
Stable Solutions LLC Department of Surgery
Easton Industrial Park UMass Memorial Medical Center
Easton, MA Worcester, MA

Cathy Dudick, MD, FACS Jennifer L. Englund, MD


Medical Director, Surgical Intensive Care Unit Medical Toxicology Fellow
Department of Surgery Department of Emergency Medicine
Jersey Shore University Medical Center Division of Medical Toxicology
Neptune, NJ University of Massachusetts Medical School
Worcester, MA
David L. Dunn, MD, PhD
Vice President for Health Sciences Robert M. Esterl Jr, MD
Professor of Surgery, Microbiology and Immunology Professor of Surgery
University at Buffalo, School of Medicine Biomedical Sciences Department of Surgery
Buffalo, NY University of Texas Health Science Center at
San Antonio
Cheryl H. Dunnington, RN, MS, CCRN San Antonio, TX
Operations Director, eICU Support Center Program
Critical Care Operations Salomao Faintuch, MD, MSc
UMass Memorial Medical Center Instructor in Radiology
Worcester, MA Harvard Medical School
Department of Interventional Radiology
Kevin Dwyer, MD, FACS Beth Israel Deaconess Medical Center
Director of Trauma Boston, MA
Vice-Chair of Surgery
Stamford Hospital Pang-Yen Fan, MD
Stamford, CT Associate Professor of Medicine
Division of Renal Medicine
Steven B. Edelstein, MD University of Massachusetts Medical School
Professor of Anesthesiology Medical Director, Renal Transplant Program
Vice-Chairman Education & Compliance UMass Memorial Medical Center
Department of Anesthesiology Worcester, MA
Loyola University Medical Center
Loyola University Stritch School of Medicine James C. Fang, MD
Maywood, IL Professor of Medicine
Cardiovascular Division
W. Thomas Edwards, PhD, MD Case Western Reserve University
Director, Fellowship in Pain Medicine Cleveland, OH
Associate Professor of Anesthesiology
Department of Anesthesiology John Fanikos, RPh, MBA
University of Washington Assistant Director of Pharmacy
Harborview Medical Center Department of Pharmacy
Seattle, WA Brigham and Womens Hospital
Boston, MA
Richard T. Ellison III, MD
Professor of Medicine, Molecular Genetics and Harrison W. Farber, MD
Microbiology Professor of Medicine
University of Massachusetts Medical School Department of Pulmonary Center
Department of Medicine Boston University School of Medicine
Division of Infectious Diseases and Immunology Boston, MA
UMass Memorial Medical Center
Worcester, MA Khaldoun Faris, MD
Associate Director of Surgical Intensive Care Unit
Ashkan Emadi, MD, PhD Department of Anesthesiology
Adjunct Faculty University of Massachusetts Medical School
Division of Adult Hematology UMass Memorial Medical Center
Department of Internal Medicine Worcester, MA
Johns Hopkins Hospital
Johns Hopkins University Alan P. Farwell, MD
Baltimore, MD Associate Professor of Medicine
Director, Endocrine Clinics
Charles H. Emerson, MD Department of Endocrinology, Diabetes and
Professor Emeritus of Medicine Nutrition
Department of Medicine Boston University School of Medicine
UMass Memorial Medical Center Boston Medical Center
Worcester, MA Boston, MA
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Contributors xi

Alan M. Fein, MD, FACP, FCCP, FCCM Joseph J. Frassica, MD


Clinical Professor of Medicine VP and Chief Medical Information Officer
Chief of Pulmonary, Sleep and Critical Care Medicine Philips Healthcare
Hofstra North ShoreLIJ School of Medicine Senior Consultant Massachusetts General Hospital
ProHEALTH Care Associates, LLP Research Affiliate Massachusetts Institute of Technology
Lake Success, NY Cambridge, MA

Philip Fidler, MD, FACS R. Brent Furbee, MD


Associate Director, Burn Center Medical Director
Department of Surgery Indiana Poison Center
Washington Hospital Center Indiana University Health Methodist Hospital
Washington, DC Indianapolis, IN

Michael A. Fifer, MD Shrawan G. Gaitonde, MD


Director, Cardiac Catheterization Laboratory Surgery Resident
Division of Cardiology Department of Surgery
Department of Medicine University Hospital/University of Cincinnati
Massachusetts General Hospital Cincinnati, OH
Boston, MA
Richard L. Gamelli, MD, FACS
Robert W. Finberg, MD Dean, Stritch School of Medicine
Professor and Chair, Department of Medicine Loyola University Chicago
University of Massachusetts Medical School Senior Vice President
Department of Medicine Loyola University Medical Center
UMass Memorial Medical Center Maywood, IL
Worcester, MA
Michael Ganetsky, MD
Kimberly A. Fisher, MD Clinical Instructor, Harvard Medical School
Assistant Professor of Medicine Clinical Director, Division of Medical Toxicology
University of Massachusetts Medical School Department of Emergency Medicine
UMass Memorial Medical Center Beth Israel Deaconess Medical Center
Worcester, MA Boston, MA

Marc Fisher, MD Joseph J. Gard, MD


Professor of Neurology Cardiology Fellow
University of Massachusetts Medical School Department of Internal Medicine
UMass Memorial Medical Center Division of Cardiovascular Diseases
Worcester, MA Mayo Clinic
Rochester, MN
Patrick F. Fogarty, MD
Director, Penn Comprehensive Hemophilia and James Geiling, MD, FACP, FCCP, FCCM
Thrombosis Program Professor of Medicine
Department of Medicine Dartmouth Medical School
University of Pennsylvania Hanover, NH;
Philadelphia, PA Chief, Medical Service
VA Medical Center
Dorrie K. Fontaine, PhD, RN, FAAN White River Junction, VT
Dean and Professor
School of Nursing Debra Gerardi, RN, MPH, JD
University of Virginia CEO
Charlottesville, VA EHCCO, LLC
Principal, Debra Gerardi and Associates
Nancy M. Fontneau, MD Half Moon Bay, CA
Associate Professor of Clinical Neurology
University of Massachusetts Medical School Edith S. Geringer, MD
UMass Memorial Medical Center Psychiatrist
Worcester, MA Department of Psychiatry
Massachusetts General Hospital
Marsha D. Ford, MD Boston, MA
Director, Carolinas Poison Center
Department of Emergency Medicine Terry Gernsheimer, MD
Carolinas Medical Center Medical Director of Transfusion
Charlotte, NC Seattle Cancer Care Alliance and University of
Washington Medical Center
Keith J. Foster, PharmD, BCPS Professor of Medicine
Clinical Pharmacist Surgical Intensive Care Unit Division of Hematology
Department of Pharmacy Puget Sound Blood Center
UMass Memorial Medical Center Department of Medical Education
Worcester, MA Seattle, WA
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xii Contributors

John G. Gianopoulos, MD Damian J. Green, MD


System Chair of Maternal/Fetal Medicine Research Associate
Department of OB/GYN Clinical Research Division
Cook County Health and Hospital System Fred Hutchinson Cancer Research Center
Chicago, IL Seattle, WA

Michael M. Givertz, MD Bruce Greenberg, MD


Associate Professor of Medicine Assistant Professor
Harvard Medical School Department of Medicine
Medical Director, Heart Transplant and Circulatory University of Massachusetts Medical School
Assist Program Worcester, MA
Cardiovascular Division
Brigham and Womens Hospital Bonnie C. Greenwood, PharmD, BCPS
Boston, MA Staff Development and Perioperative Services Manager
Department of Pharmacy
Richard H. Glew, MD Brigham and Womens Hospital
Professor of Medicine, Molecular Genetics and Boston, MA
Microbiology
Vice Chair, MedicineUndergraduate Medical Ronald F. Grossman, MD
Education and Faculty Affairs Professor of Medicine
Department of Medicine University of Toronto
UMass Memorial Medical Center Credit Valley Hospital
Worcester, MA Mississauga, Ontario, Canada

Dori Goldberg, MD Rainer W.G. Gruessner, MD


Assistant Professor of Medicine Professor of Surgery
Division of Dermatology Department of Surgery
Department of Medicine University of Arizona
University of Massachusetts Medical School Tucson, AZ
UMass Memorial Medical Center
Worcester, MA Chandra Prakash Gyawali, MD, MRCP
Associate Professor of Medicine
Andrew J. Goodwin, MD Division of Gastroenterology
Clinical and Research Fellow Department of Medicine
Department of Pulmonary and Critical Care Washington University School of Medicine
Brigham and Womens Hospital Barnes-Jewish Hospital
Boston, MA St. Louis, MO

Ammar Habib, MD
Kim L. Goring, MMBS
Internal Medicine Resident
Assistant Professor of Medicine
Department of Internal Medicine
Department of Internal Medicine
Mayo Clinic
Division of Pulmonary, Critical Care and Sleep Medicine
Rochester, MN
Howard University Hospital
Washington, DC
Shirin Haddady, MD
Assistant Professor of Medicine and Neurology
Robert M. Gougelet, MD Department of Medicine
Assistant Professor of Medicine (Emergency Medicine) University of Massachusetts Medical School
Director, New England Center of Emergency Preparedness UMass Memorial Medical Center
Department of Emergency Medicine Worcester, MA
Dartmouth Hitchcock Medical Center
Lebanon, NH Pegge M. Halandras, MD
Assistant Professor
Andis Graudins, MBBS, PhD, FACEM, FACMT Department of Surgery
Professor of Emergency Medicine Research and Division of Vascular Surgery and Endovascular
Clinical Toxicology Therapy
Faculty of Medicine Nursing and Health Sciences Loyola University Chicago Stritch School of Medicine
Monash University Maywood, IL
Department of Emergency Medicine
Monash Medical Centre Wiley R. Hall, MD
Clayton, Victoria, Australia Assistant Professor in Neurology and Surgery
Director of Neuroscience Critical Care
Barth A. Green, MD University of Massachusetts Medical School
Professor and Chairman Medical Director of the Neuro/Trauma ICU
Department of Neurological Surgery Neurology Department
Jackson Memorial/University of Miami UMass Memorial Medical Center
Miami, FL Worcester, MA
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Contributors xiii

Stephen B. Hanauer, MD Thomas L. Higgins, MD, MBA, FACP, FCCM


Professor of Medicine and Clinical Pharmacology Professor of Medicine
Department of Gastroenterology Department of Anesthesia and Surgery
University of Chicago Interim Chair
Chicago, IL Department of Medicine
Baystate Medical Center
Charles William Hargett, III, MD Springfield, MA
Associate in Medicine
Division of Pulmonary & Critical Care Nicholas Hill, MD
Duke University Medical Center Chief
Durham, NC Department of Pulmonary, Critical Care and Sleep Division
Tufts Medical Center
Boston, MA
David M. Harlan, MD
Chief, Diabetes Division John B. Holcomb, MD, FACS
Co-Director, Diabetes Center of Excellence Vice Chair and Professor
Department of Medicine Department of Surgery
UMass Memorial Medical Center Memorial Hermann Hospital
University of Massachusetts School of Medicine Houston, TX
Worcester, MA
Judd E. Hollander, MD
Laura Harrell, MD, MS Professor, Clinical Research Director
Assistant Professor of Medicine Department of Emergency Medicine
Department of Gastroenterology Hospital of the University of Pennsylvania
University of Chicago Medical Center Philadelphia, PA
Chicago, IL
Helen M. Hollingsworth, MD
Lawrence J. Hayward, MD, PhD Associate Professor of Medicine
Professor of Neurology Department of Pulmonary Allergy and Critical
Department of Neurology Care Medicine
University of Massachusetts Medical School Boston Medical Center
Worcester, MA Boston, MA

Kennon Heard, MD Shelley A. Holmer, MD


Associate Professor Clinical Associate
Rocky Mountain Poison and Drug Center, Department of Psychiatry
Denver Health Duke University Medical Center
Department of Emergency Medicine Durham, NC
University of Colorado School of Medicine
Denver, CO Donough Howard, MD
Consultant Rheumatologist
Stephen O. Heard, MD Hermitage Medical Clinic
Dublin, Ireland
Professor and Chair
University of Massachusetts Medical School
Department of Anesthesiology Michael D. Howell, MD, MPH
UMass Memorial Medical Center Director, Critical Care Quality
Worcester, MA Beth Israel Deaconess Medical Center
Boston, MA
John E. Heffner, MD Rolf D. Hubmayr, MD
Garnjobst Chair and Professor of Medicine
Professor
Department of Medicine
Department of Medicine and Physiology
Providence Portland Medical Center
Mayo Clinic
Portland, OR
Rochester, MN

Jeremy S. Helphenstine, DO Abhinav Humar, MD


Clinical Instructor Professor of Surgery
Toxicology Fellow Division Chief, Transplant Surgery
Department of Emergency Medicine Department of Surgery
Emory School of Medicine University of Pittsburgh
Atlanta, GA Pittsburgh, PA

Robert J. Heyka, MD Thomas L. Husted, MD


Director, Outpatient Hemodialysis Assistant Professor of Surgery
Department of Nephrology & Hypertension Department of Surgery
Cleveland Clinic Foundation University of Cincinnati
Cleveland, OH Cincinnati, OH
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xiv Contributors

Richard S. Irwin, MD, Master FCCP Thanjira Jiranantakan, MD


Professor of Medicine and Nursing Preventive and Social Medicine Department
University of Massachusetts Siriraj Hospital Faculty of Medicine
Chair, Critical Care Mahidol University, Thailand
UMass Memorial Medical Center Medical Toxicology Fellow
Worcester, MA Department of Clinical Pharmacology and Medical
Toxicology
San Francisco General Hospital, University of
John M. Iskander California
Fellow in Gastroenterology The California Poison Control SystemSan Francisco
Division of Gastroenterology Division
St. Louis, MO San Francisco, CA

Paul G. Jodka, MD
Eric M. Isselbacher, MD Assistant Professor of Medicine and
Professor of Medicine Anesthesiology
Harvard Medical School Tufts University School of Medicine
Co-Director, Thoracic Aortic Center Adult Critical Care Division
Massachusetts General Hospital Baystate Medical Center
Boston, MA Springfield, MA

Rao R. Ivatury, MD Scott B. Johnson, MD, FACS, FCCP


Chair Associate Professor
Department of Surgery Chief of General Thoracic Surgery
Division of Trauma, Critical Care, Emergency Department of Cardiothoracic Surgery
Surgery University of Texas Health Science Center,
Virginia Commonwealth University San Antonio
Richmond, VA San Antonio, TX

Sreenivasa S. Jonnalagadda, MD, FASGE


William L. Jackson Jr, MD, MBA Professor of Medicine
Medical Director, Adult Critical Care Director of Pancreatic and Biliary Endoscopy
Inova Health System Washington University School of Medicine
Falls Church, VA Division of Gastroenterology
St. Louis, MO

Eric W. Jacobson, MD
Bryan S. Judge, MD
Associate Professor of Medicine
University of Massachusetts Medical School Associate Program Director
Senior Vice President, Clinical Research and Assistant Professor
Regulatory Affairs Spectrum Health
Chief Medical Officer Grand Rapids MERC/Michigan State University
Synta Pharmaceuticals Corp. Program in Emergency Medicine
Lexington, MA Grand Rapids, MI

Eias E. Jweied, MD, PhD


Donald H. Jenkins, MD, FACS Cardiovascular/Thoracic Surgeon
Trauma Director Department of Cardiothoracic and Vascular Surgical
Associate Professor of Surgery Associates, S.C.
Division of Trauma, Critical Care and Emergency Advocate Christ Medical Center
General Surgery Oak Lawn, IL
Mayo Clinic
Rochester, MN
Marc J. Kahn, MD
Professor of Medicine
Jing Ji, MD SR. Associate Dean
Department of Medicine
Neurology Resident
Tulane University School of Medicine
Department of Neurology
New Orleans, LA
University of Massachusetts Medical School
Worcester, MA
Raja Kandaswamy, MD
Axline Professor of Surgery
Tun Jie, MD, MS Director of the University of Florida Institute of
Assistant Professor of Surgery Transplantation
Department of Surgery Department of Surgery
University of Arizona, College of Medicine Shands HospitalUniversity of Florida Gainesville
Tucson, AZ Gainesville, FL
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Contributors xv

Abhishek Katiyar, MD Stephen J. Krinzman, MD


Medical and Toxicology and Emergency Medicine Assistant Professor of Medicine
Department of Emergency Medicine Division of Pulmonary, Allergy, and Critical
UIC/Advocate Christ Hospital Care Medicine
Oak Lawn, IL University of Massachusetts Medical School
UMass Memorial Medical Center
Carol A. Kauffman, MD Worcester, MA
Professor Internal Medicine
University of Michigan Medical School Gowri Kularatna, MD
Chief, Infectious Diseases Fellow in Gastroenterology
Veterans Affairs Ann Arbor Healthcare Washington University School of Medicine/Barnes Jewish
System Hospital
Ann Arbor, MI Division of Gastroenterology
St. Louis, MO
Christoph R. Kaufmann, MD, MPH
Professor of Surgery, East Tennessee State University Sonal Kumar, MD
Department of Trauma and Emergency Surgery Internal Medicine Resident
Johnson City Medical Center Department of Internal Medicine
Johnson City, TN Barnes Jewish Hospital
St. Louis, MO
Shubjeet Kaur, MD
Clinical Professor and Vice Chair Margaret Laccetti, PhD, RN, AOCN, ACHPN
Department of Anesthesiology Director, Nursing Professional Development
University of Massachusetts Medical School UMass Memorial Medical Center
UMass Memorial Medical Center Worcester MA
Worcester, MA
Hoa Thi Lam, BS
Glenn Kershaw, MD Research Assistant
Associate Professor of Clinical Medicine Department of Child Psychiatry
Division of Renal Medicine Massachusetts General Hospital
University of Massachusetts Medical School Boston, MA
UMass Memorial Medical Center
Worcester, MA Robert A. Lancy, MD, MBA
Chief of Cardiac Surgery
Mark A. Kirk, MD Department of Cardiac Surgery
Medical Toxicology Fellowship Director Bassett Medical Center
Department of Emergency Medicine Cooperstown, NY
University of Virginia
Charlottesville, VA Angeline A. Lazarus, MD
Professor of Medicine
Meghan S. Kolodziej, MD Department of Pulmonary Medicine
Instructor in Psychiatry Division of Pulmonary
Department of Psychiatry National Naval Medical Center
Brigham and Womens Hospital Bethesda, MD
Boston, MA
Jason Lee-Llacer, MD
Scott E. Kopec, MD Fellow
Assistant Professor of Medicine Department of Critical Care Medicine and Anesthesia
Division of Pulmonary, Allergy and Critical George Washington University
Care Medicine Washington, DC
UMass Memorial Medical Center
University of Massachusetts Medical School Anthony J. Lembo, MD
Worcester, MA Associate Professor of Medicine
Department of Medicine
Bruce A. Koplan, MD Beth Israel Deaconess Med Center
Assistant Professor of Medicine Boston, MA
Harvard Medical School
Cardiac Arrhythmia Service James A. de Lemos, MD
Department of Cardiac Arrhythmia CCU and Cardiology Fellowship Director
Brigham and Womens Hospital Department of Cardiology/Medicine
Boston, MA The University of Texas Southwestern Medical Center
Dallas, TX
Richard Kremsdorf, MD
Clinical Professor of Medicine, Voluntary Adam B. Lerner, MD
University of California, San Diego School of Medicine Director, Cardiac Anesthesia
President Department of Anesthesia and Critical Care
Five Rights Consulting, Inc. Beth Israel Deaconess Medical Center
San Diego, CA Boston, MA
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xvi Contributors

Phillip A. Letourneau, MD Mark S. Link, MD


Research Fellow/General Surgery Resident Professor of Medicine
Department of Surgery Department of Cardiac Electrophysiology
University of Texas Medical School at Houston Tufts Medical Center
Houston, TX Boston, MA

Howard B. Levene, MD, PhD Carol F. Lippa, MD


Assistant Professor of Neurological Surgery Professor of Neurology
Department of Neurosurgery Department of Neurology
University of Miami Hospital Drexel University College of Medicine
Miami, FL Philadelphia, PA
Nikki A. Levin, MD, PhD
Associate Professor of Medicine Alan Lisbon, MD
Division of Dermatology Associate Professor, Anaesthesia, Harvard
University of Massachusetts Medical School Medical School
Worcester, MA Department of Anaesthesia, Critical Care and
Pain Medicine
Stephanie M. Levine, MD Beth Israel Deaconess Medical Center
Professor of Medicine Boston, MA
Department of Medicine
University of Texas Health Science Center at San Antonio Mauricio Lisker-Melman, MD
San Antonio, TX Professor of Medicine
Director, Hepatology Program
William J. Lewander, MD Department of Internal Medicine
Professor and Associate Vice Chair of Pediatric Emergency Division of Gastroenterology
Medicine Washington University School of Medicine
The Warren Alpert Medical School of Brown University Barnes-Jewish Hospital
Department of Emergency Medicine St. Louis, MO
Rhode Island Hospital
Providence, RI
N. Scott Litofsky, MD, FACS
Daniel H. Libraty, MD Professor and Chief
Associate Professor Director of Neuro-Oncology and Radiosurgery
Department of Medicine/Infectious Diseases Division of Neurological Surgery
University of Massachusetts Medical School University of Missouri School of Medicine
Worcester, MA Columbia, MO

Craig M. Lilly, MD Afroza Liton, MD


Professor of Medicine, Anesthesiology and Fellow
Surgery Department of Infectious Disease
Department of Medicine University of Massachusetts
University of Massachusetts Medical School UMass Memorial Medical Center
UMass Memorial Medical Center Worcester, MA
Worcester, MA

Sonia Lin, PharmD, BCPS Frederic F. Little, MD


Clinical Pharmacy Specialist Assistant Professor of Medicine
Department of Pharmacy Pulmonary Center and Department of Pulmonary,
University of Colorado Hospital Allergy, and Critical Care Medicine
Aurora, CO Boston University School of Medicine
Attending Physician
Christopher H. Linden, MD Boston Medical Center
Professor, Department of Emergency Medicine Boston, MA
Division of Medical Toxicology
University of Massachusetts Medical School Nancy Y.N. Liu, MD
UMass Memorial Medical Center Associate Professor of Clinical Medicine
Worcester, MA Department of Medicine
Division of Rheumatology
Michael Linenberger, MD, FACP University of Massachusetts Medical School
Professor, Division of Hematology Worcester, MA
Department of Medicine
University of Washington
Associate Member, Clinical Research Division Randall R. Long, MD, PhD
Fred Hutchinson Cancer Research Center Cheshire Medical Center/Dartmouth
Seattle Cancer Care Alliance Hitchcock Keene
Seattle, WA Keene, NH
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Contributors xvii

Robert B. Love, MD, FACS Avinash V. Mantravadi, MD


Professor and Vice Chairman Resident Physician
Department of Thoracic and Cardiothoracic Department of OtolaryngologyHead and Neck Surgery
Loyola University Medical Center Loyola University Medical Center
Maywood, IL Maywood, IL

Matthew W. Lube, MD Paul E. Marik, MD, FCCM, FCCP


Assistant Professor of Surgery and Surgical Clerkship Professor of Medicine
Director Department of Pulmonary and Critical Care Medicine
University of Central Florida College of Medicine Eastern Virginia Medical School and Norfolk General
Associate Director of Medical Education Hospital
Department of Surgical Education Eastern Virginia Medical School Internal Medicine
Orlando Regional Medical Center Norfolk, VA
Orlando, FL
William L. Marshall, MD
Fred A. Luchette, MD, MSc Associate Professor of Medicine
The Ambrose and Gladys Bowyer Professor of Surgery Department of Medicine
Stritch School of Medicine UMass Memorial Medical Center
Medical Director, General Surgery III Service Worcester, MA
Department of Surgery
Maywood, IL Arthur J. Matas, MD
Professor of Surgery
Department of Surgery
Alice D. Ma, MD University of Minnesota
Associate Professor of Medicine Minneapolis, MN
Department of Medicine
Division Hematology/Oncology Paul H. Mayo, MD
University of North Carolina
Professor of Clinical Medicine
Chapel Hill, NC
Hofstra NorthshoreLIJ School of Medicine
Long Island Jewish Medical Center
Theresa R. (Roxie) Macfarlan, RN, MSN, CCRN, New Hyde Park, NY
ACNP-BC
Advanced Practice Nurse 2 Guy Maytal, MD
Department of Thoracic-Cardiovascular Postoperative Director of Urgent Care and Primary Care Psychiatry
Intensive Care Unit Department of Psychiatry
University of Virginia Health System Massachusetts General Hospital
Charlottesville, VA Boston, MA

J. Mark Madison, MD Melanie Maytin, MD


Professor of Medicine and Physiology Instructor in Medicine
Chief, Division of Pulmonary, Allergy and Critical Care Department of Cardiovascular Medicine
Medicine Brigham and Womens Hospital
UMass Memorial Medical Center Boston, MA
University of Massachusetts Medical School
Worcester, MA Kathleen M. McCauley, PhD, RN, ACNS-BC,
FAAN, FAHA
Ajai K. Malhotra, MBBS, MD, MS, DNB, FRCS Associate Dean for Academic Programs
Associate Professor and Vice Chair Class of 1965 25th Reunion Term Professor of
Associate Medical Director, Level 1 Trauma Center Cardiovascular Nursing
Department of Surgery Cardiovascular Clinical Specialist
Division of Trauma, Critical Care and Emergency General University of Pennsylvania School of Nursing
Surgery Hospital of the University of Pennsylvania
Virginia Commonwealth University Medical Center Philadelphia, PA
Richmond, VA
Sara L. Merwin, MPH
Assistant Professor of Medicine
Atul Malhotra, MD
Department of Medicine
Associate Professor of Medicine Hofstra North ShoreLIJ School of Medicine
Department of Medicine North Shore University Hospital
Brigham and Womens Hospital Manhasset, NY
Boston, MA
Marco Mielcarek, MD
Samir Malkani, MD Assistant Professor
Clinical Associate Professor of Medicine University of Washington
Division of Diabetes Assistant Member
Department of Medicine Department of Medical Oncology
UMass Memorial Medical Center Fred Hutchinson Cancer Research Center
Worcester, MA Seattle, WA
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xviii Contributors

Ross Milner, MD James B. Mowry, PharmD, DABAT, FAACT


Associate Professor of Surgery Director, Indiana Poison Center
Chief, Division of Vascular Surgery and Endovascular Department of Emergency Medicine and
Therapy Trauma Center
Department of Vascular Surgery Methodist Hospital, Indiana University Health
Loyola University Medical Center Indianapolis, IN
Maywood, IL
Saori A. Murakami, MD
Ann L. Mitchell, MD Psychiatrist
Associate Professor of Clinical Neurology Massachusetts General Hospital, McLean Hospital
Department of Neurology Boston, MA
University of Massachusetts Medical School
UMass Memorial Medical Center Michael C. Muzinich, MD
Worcester, MA Neurosurgical Resident
Department of Neurological Surgery
University Hospital and Clinics
Lawrence C. Mohr Jr, MD, ScD, FACP, FCCP Columbia, MO
Professor of Medicine, Biometry and Epidemiology
Director, Environmental Biosciences Program
Medical University of South Carolina
John G. Myers, MD
Charleston, SC Associate Professor
Department of Surgery
University of Texas Health Science Center, San Antonio
Takki Momin, MD San Antonio, TX
Vascular Surgery Fellow
Department of Vascular Surgery Shashidhara Nanjundaswamy, MD, MBBS,
Georgetown University/Washington MRCP, DM
Hospital Center Assistant Professor
Washington, DC Department of Neurology
University of Massachusetts Medical School
Jahan Montague, MD Worcester, MA
Assistant Professor of Medicine
Department of Nephrology Lena M. Napolitano, MD, FACS, FCCP, FCCM
UMass Memorial Medical Center Professor of Surgery
Worcester, MA Department of Surgery
University of Michigan
Ann Arbor, MI
Bruce Montgomery, MD
Associate Professor Jaishree Narayanan, MD, PhD
Department of Medicine, Oncology
Associate Professor Clinical Neurology
University of Washington
Department of Neurology
VA Puget Sound HCS
UMass Memorial Medical Center
Seattle, WA
Worcester, MA

Majaz Moonis, MD, MRCP(1), DM, Theresa A. Nester, MD


FRCP (Edin) Associate Medical Director
Professor of Neurology Puget Sound Blood Center
Director, Stroke Services Department of Laboratory Medicine
Director, Vascular Fellowship Program University of Washington Medical Center
UMass Memorial Medical Center Puget Sound Blood Center
Worcester, MA Seattle, WA

Michael S. Niederman, MD
John P. Mordes, MD
Professor of Medicine
Professor of Medicine
SUNY at Stony Brook
Department of Medicine/Endocrinology Chairman, Department of Medicine
UMass Memorial Medical Center
Winthrop-University Hospital
University of Massachusetts Medical School
Mineola, NY
Worcester, MA
Dominic J. Nompleggi, MD, PhD
David A. Morrow, MD, MPH Associate Professor of Medicine and Surgery
Director, Samuel A. Levine Cardiac Unit University of Massachusetts Medical School
Department of Cardiovascular Medicine Chief, Division of Gastroenterology
Brigham and Womens Hospital Director, Adult Nutrition Support Service
Harvard Medical School UMass Memorial Medical Center
Boston, MA Worcester, MA
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Contributors xix

Sean E. Nork, MD Mickey M. Ott, MD


Associate Professor Assistant Professor in Surgery
Department of Orthopaedics & Sports Medicine Division of Trauma & Surgical Critical Care
Harborview Medical Center, University of Vanderbilt University Medical Center
Washington Nashville, TN
Seattle, WA
John A. Paraskos, MD
Robert L. Norris, MD, FACEP
Professor of Medicine
Associate Professor
Department of Medicine
Department of Surgery University of Massachusetts Medical School
Chief, Division of Emergency Medicine
UMass Memorial Medical Center
Stanford University Medical Center Worcester, MA
Palo Alto, CA

Richard A. Oeckler, MD, PhD Polly E. Parsons, MD


Assistant Professor of Medicine and Physiology Professor and Chair of Medicine
Department of Pulmonary and Critical Care Medicine Department of Medicine
Mayo Clinic University of Vermont College of Medicine
Rochester, MN Fletcher Allen Health Care
Burlington, VT

Patrick T. OGara, MD
Executive Medical Director of the Carl J. and Laura Santos Pavia, MD
Ruth Shapiro Cardiovascular Center Resident in Anesthesiology
Associate Professor Boston Medical Center
Harvard Medical School Boston University School of Medicine
Director, Clinical Cardiology Boston, MA
Brigham and Womens Hospital
Boston, MA Marie T. Pavini, MD, FCCP
Intensivist
Paulo J. Oliveira, MD, FCCP Department of Intensive Care Unit
Director, Advanced Bronchoscopic and Rutland Regional Medical Center
Pleural Procedures Rutland, VT
Assistant Professor of Medicine
Division of Pulmonary, Allergy and Critical David Paydarfar, MD
Care Medicine
Professor of Neurology and Physiology
UMass Memorial Medical Center
Department of Neurology
Worcester, MA
University of Massachusetts Medical School
Worcester, MA
Kent R. Olson, MD, FACEP, FAACT, FACMT
Medical Director, San Francisco Division
California Poison Control System
William D. Payne, MD
Clinical Professor of Medicine and Pharmacy Professor of Surgery
University of California, San Francisco Director, Liver Transplant
San Francisco, CA Department of Surgery
University of Minnesota
Minneapolis, MN
Steven M. Opal, MD
Professor of Medicine
Warren Alpert Medical School of Brown University Randall S. Pellish, MD
Memorial Hospital of Rhode Island Assistant Professor of Medicine
Division of Infectious Disease Division of Gastroenterology
Pawtucket, RI University of Massachusetts Medical School
Worcester, MA
Achikam Oren-Grinberg, MD, MS
Director of Critical Care Echocardiography Alexis C. Perkins, MD
Department of Anesthesia, Critical Care & Chief Resident
Pain Medicine Department of Dermatology
Beth Israel Deaconess Medical Center University of Massachusetts Medical School
Boston, MA Worcester, MA

David Ost, MD, MPH Catherine A. Phillips, MD


Associate Professor Associate Professor of Clinical Neurology
Department of Pulmonary Medicine University of Massachusetts Medical School
The University of Texas M.D. Anderson Cancer Department of Neurology
Center UMass Memorial Medical Center
Houston, TX Worcester, MA
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xx Contributors

Ryan F. Porter, MD John Querques, MD


Resident Physician Assistant Professor of Psychiatry
Department of Internal Medicine Harvard Medical School
Washington University School of Medicine Associate Director, Psychosomatic MedicineConsultation
Barnes-Jewish Hospital Psychiatry Fellowship Program
St. Louis, MO Department of Psychiatry
Massachusetts General Hospital
Louis G. Portugal, MD, FACS Boston, MA
Associate Professor of Surgery
Department of Surgery Sunil Rajan, MD, FCCP
The University of Chicago Department of Medicine
Chicago, IL Pulmonary Medicine and Critical Care
Pulmonary Associates of Richmond, Inc.
Joseph A. Posluszny Jr, MD Midlothian, VA
Research Fellow
Department of Burn and Shock Trauma Institute Paula D. Ravin, MD
Loyola University Medical Center
Associate Professor of Clinical Neurology
Maywood, IL
Department of Neurology
UMass Memorial Medical Center
Melvin R. Pratter, MD Worcester, MA
Head, Division of Pulmonary and Critical Care Medicine
Department of Medicine
Cooper University Hospital Justin L. Regner, MD
Camden, NJ Assistant Professor of Surgery
Division of Trauma and Critical Care
David J. Prezant, MD University of Arkansas Medical School
Little Rock, AR
Chief Medical Officer
Special Advisor to the Fire Commissioner for Health Policy
Co-Director WTC Medical Monitoring & Treatment Harvey S. Reich, MD, FACP, FCCP
Programs Director, Critical Care Medicine
New York City Fire Department Department of Critical Care Medicine
Professor of Medicine Rutland Regional Medical Center
Albert Einstein College of Medicine Rutland, VT
Pulmonary Division
Brooklyn, NY Randall R. Reves, MD, MSc
Medical Director of the Denver Metro Tuberculosis
Timothy A. Pritts, MD, PhD
Control Program
Associate Professor of Surgery Department of Medicine and Public Health
Department of Surgery Denver Public Health Department
Division of Trauma and Critical Care Denver, CO
University of Cincinnati
Cincinnati, OH
John Ricotta, MD, FACS
John T. Promes, MD Professor of Surgery, Georgetown University
Director, Trauma Services Harold H. Hawfield Chair of Surgery
Department of Medical Center Department of Surgery
Orlando Regional Medical Center Washington Hospital Center
Orlando, FL Washington, DC

Donald S. Prough, MD Teresa A. Rincon, BSN, RN, CCRN-E


Professor and Chair Nurse Director
Anesthesiology Sutter Health System
UTMB Anesthesiology Sacramento-Sierra Region eICU
Galveston, TX Sacramento, CA

Leon M. Ptaszek, MD, PhD


Clinical Fellow Ray Ritz, BA, RRT, FAARC
Department of Medicine Director of Respiratory Care
Cardiology Division Department of Respiratory Care
Massachusetts General Hospital Beth Israel Deaconess Medical Center
Boston, MA Boston, MA

Juan Carlos Puyana, MD Kimberly A. Robinson, MD, MPH


Associate Professor of Surgery Assistant Professor of Medicine
Department of Surgery Division of Pulmonary, Critical Care
University of Pittsburgh Medical Center Marlborough Hospital
Pittsburgh, PA Marlborough, MA
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Contributors xxi

Mark J. Rosen, MD Michael G. Seneff, MD


Division of Pulmonary, Critical Care and Sleep Medicine Associate Professor
North Shore University and Long Island Jewish Health Department of Anesthesiology and Critical
System Care Medicine
Professor of Medicine The George Washington University Hospital
Hofstra North ShoreLong Island Jewish School of Washington, DC
Medicine
New Hyde Park, NY M. Michael Shabot, MD
System Chief Medical Officer
Aldo A. Rossini, MD Department of Executive Officers
Professor of Medicine Memorial Hermann Healthcare System
Emeritus Houston, TX
Department of Medicine
University of Massachusetts Medical School Violet L. Shaffer, MA, BA
Worcester, MA Research Vice President and Global Industry
Service Director
Alan L. Rothman, MD Department of Research
Professor Gartner, Inc.
Department of Medicine Stamford, CT
UMass Memorial Medical Center
Worcester, MA Samir R. Shah, MD
Plastic Surgery Fellow
Marc S. Sabatine, MD, MPH Department of Plastic Surgery
Vice Chair TIMI Study Group Loyola University Medical Center
Associate Professor of Medicine Maywood, IL
Harvard Medical School
Associate Cardiologist
Division of Cardiovascular Medicine
Sajid Shahul, MD
Brigham and Womens Hospital Assistant Program Director
Boston, MA Associate Director Cardiac Surgical Intensive
Care Unit
Beth Israel Deaconess Medical Center
Marjorie S. Safran, MD Harvard Medical School
Professor of Clinical Medicine Boston, MA
Department of Endocrinology
University of Massachusetts Medical School
UMass Memorial Medical Center Michael W. Shannon, MD, MPH, FAAP,
Worcester MA FACEP (DECEASED)
Chief and Chair, Division of Emergency
Steven A. Sahn, MD Medicine
Professor of Medicine and Division Director Director, Center for Biopreparedness
Division of Pulmonary, Critical Care, Allergy and Co-Director, Pediatric Environmental
Sleep Medicine Health Center
The Medical University of South Carolina Professor of Pediatrics, Harvard Medical School
Charleston, SC Childrens Hospital Boston
Division of Emergency Medicine
Todd W. Sarge, MD Boston, MA
Instructor in Anaesthesia
Harvard Medical School Richard D. Shih, MD
Department of Anesthesia, Critical Care and Emergency Medicine Program Director
Pain Medicine Department of Emergency Medicine
Beth Israel Deaconess Medical Center Morristown Memorial Hospital
Boston, MA Morristown, NJ

Benjamin M. Scirica, MD, MPH Andrew F. Shorr, MD, MPH


Associate Physician and Investigator Associate Director, Pulmonary and Critical Care
Department of Medicine Department of Medicine
Cardiovascular Division Washington Hospital Center
TIMI Study Group Washington, DC
Brigham and Womens Hospital
Boston, MA Sara J. Shumway, MD
Professor of Cardiothoracic Surgery
Douglas Seidner, MD Vice-Chief
Associate Professor of Medicine Division of Cardiothoracic Surgery
Division of Gastroenterology, Hepatology and Nutrition Surgical Director, Lung Transplantation
Director, Vanderbilt Center for Human Nutrition Department of Surgery
Vanderbilt University Medical Center University of Minnesota Medical Center, Fairview
Nashville, TN Minneapolis, MN
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xxii Contributors

Samy S. Sidhom, MD, MPH Howard G. Smith, MD, FACS


Clinical Associate Director of Burn Services
Tufts University School of Medicine Orlando Regional Medical Center
Clinical Fellow Associate Professor of Surgery
Division of Pulmonary, Critical Care and Sleep University of Central Florida College of Medicine
Medicine Orlando, FL
Tufts Medical Center
Boston, MA Jason W. Smith, MD
Fellow, Cardiothoracic Surgery
Department of Cardiovascular and Thoracic
Anupam Singh, MD Surgery
Assistant Professor of Medicine, GI Hospitalist Loyola University Medical Center
Department of Medicine Maywood, IL
Division of Gastroenterology
UMass Memorial Medical Center Jennifer Smith, MD
Worcester, MA
Banner Good Samaritan Medical Center
Phoenix, AZ
Inder M. Singh, MD
Fellow Dustin L. Smoot, MD
Division of Digestive Diseases Associate Consultant
University of California, Los Angeles Department of Trauma, Critical Care and
Los Angeles, CA General Surgery
Mayo Clinic
Rochester, MN
Jagmeet P. Singh, MD, PhD
Associate Professor of Medicine Nicholas A. Smyrnios, MD
Department of Cardiac Arrhythmia Service Professor of Medicine
Massachusetts General Hospital Director, Medical Intensive Care Units
Boston, MA Division of Pulmonary, Allergy, and Critical
Care Medicine
Marco L.A. Sivilotti, MD, MSc, FRCPC, FACEP, University of Massachusetts Medical School
Worcester, MA
FACMT
Associate Professor, Department of Emergency Patrick D. Solan, MD
Medicine and of Pharmacology & Toxicology
Surgery Resident
Queens University
Department of Surgery
Kingston, Ontario, Canada
University Hospital/University of Cincinnati
Cincinnati, OH
Brian S. Smith, PharmD, BCPS
Director, Education and Clinical Services Dennis I. Sonnier, MD
Department of Pharmacy Surgery Resident
UMass Memorial Medical Center Department of Surgery
Worcester, MA University Hospital/University of Cincinnati
Cincinnati, OH
Craig S. Smith, MD Brennan M.R. Spiegel, MD, MSHS
Assistant Professor of Medicine Assistant Professor of Medicine
University of Massachusetts Medical School VA Greater Los Angeles Healthcare System
Director of Cardiac Critical Care Unit David Geffen School of Medicine at UCLA
UMass Memorial Medical Center Co-Director, Center for the Study of Digestive Healthcare
Worcester, MA Quality and Outcomes
Los Angeles, CA
Dorsett D. Smith, MD, FCCP, FACP, FACOEM
Clinical Professor of Medicine Amy E. Spooner, MD
Department of Respiratory Diseases and Critical Care Instructor in Medicine
Medicine Harvard Medical School
University of Washington Department of Medicine
Seattle, WA Division of Cardiology
Massachusetts General Hospital
Boston, MA
Heidi L. Smith, MD
Instructor of Medicine Judith A. Stebulis, MD
University of Massachusetts Medical School Assistant Professor of Medicine
Worcester, MA Department of Medicine
Director, Clinical Affairs Division of Rheumatology
Mass Biologics University of Massachusetts Medical School
Boston, MA Worcester, MA
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Contributors xxiii

Michael L. Steer, MD Joan M. Swearer, PhD, ABPP


Professor, Department of Surgery Clinical Professor of Neurology and Psychiatry
Tufts University School of Medicine Department of Neurology
Boston, MA University of Massachusetts Medical School
Worcester, MA
M. Kathryn Steiner, MD
Assistant Professor Daniel Talmor, MD, MPH
Department of Medicine Associate Professor of Anaesthesia
University of Massachusetts Medical School Department of Anesthesia, Critical Care and
UMass Memorial Medical Center Pain Medicine
Worcester, MA Beth Israel Deaconess Medical Center
Boston, MA
Jay S. Steingrub, MD, FACP, FCCP
Professor of Medicine Victor F. Tapson, MD
Tufts University School of Medicine Professor of Pulmonary and Critical Care
Boston, MA Medicine
Director of Medical Intensive Care Unit Director, Pulmonary Vascular Disease Center
Baystate Medical Center Department of Medicine
Department of Medicine Duke University Medical Center
Springfield, MA Durham, NC

Theodore A. Stern, MD Usha B. Tedrow, MD, MSc


Professor of Psychiatry in the field of Psychosomatic Director, Clinical Cardiac Electrophysiology Program
Medicine Cardiovascular Division
Consultation Brigham and Womens Hospital
Harvard Medical School Boston, MA
Chief, Psychiatric Consultation Service
Director, Office for Clinical Careers Milton Tenenbein, MD, FRCPC, FAAP, FAACT,
Department of Psychiatry FACMT
Massachusetts General Hospital Professor of Pediatrics and Pharmacology
Boston, MA Director of Emergency Services
University of Manitoba
Garrick C. Stewart, MD Childrens Hospital
Cardiovascular Medicine Fellow Winnipeg, Manitoba, Canada
Department of Cardiovascular Medicine
Brigham and Womens Hospital Jeffrey J. Teuteberg, MD
Boston, MA Associate Director, Cardiac Transplantation
Department of Cardiovascular Institute
Michael B. Streiff, MD, FACP University of Pittsburgh
Associate Professor of Medicine Pittsburgh, PA
Division of Hematology
Medical Director, Johns Hopkins Anticoagulation
Management Service and Outpatient Clinics John A. Thompson, MD
Johns Hopkins Medical Institutions Professor of Medicine
Baltimore, MD University of Washington
Seattle Cancer Care Alliance
Mark L. Sturdevant, MD Seattle, WA
Assistant Professor of Surgery
Recanati/Miller Transplant Institute Michael J. Thompson, MD
Mount Sinai Medical Center Associate Professor of Medicine
Mount Sinai College of Medicine Division of Endocrinology
New York, NY Department of Medicine
The George Washington University
David E.R. Sutherland, MD, PhD Washington, DC
Professor and Head, Division of Transplantation
Director, Diabetes Institute for Immunology and Mark Tidswell, MD
Transplantation Assistant Professor of Medicine and Surgery
Golf Classic fore Diabetes Research Chair Tufts University School of Medicine
Department of Surgery Department of Adult Critical Care
University of Minnesota Baystate Medical Center
Minneapolis, MN Springfield, MA

Colin T. Swales, MD Robert M. Tighe, MD


Associate Medical Director Medical Instructor
Transplant Division Department of Medicine
Hartford Hospital Duke University
Hartford, CT Durham, NC
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xxiv Contributors

Mira Sofia Torres, MD Javier C. Waksman, MD


Assistant Professor Associate Professor of Medicine
Fellowship Program Director Department of Medicine
Division of Endocrinology University of ColoradoDenver
University of Massachusetts Medical School Aurora, CO
UMass Memorial Medical Center
Worcester, MA J. Matthias Walz, MD, FCCP
Assistant Professor of Anesthesiology and Surgery
Ulises Torres, MD Department of Anesthesiology
Assistant Professor of Surgery Division of Critical Care Medicine
Director of Trauma Education and Outreach University of Massachusetts Medical School
Division of Trauma and Surgical Critical Care UMass Memorial Medical Center
Department of Surgery Worcester, MA
University of Massachusetts Medical School
UMass Memorial Medical Center Michael Y. Wang, MD
Worcester, MA
Associate Professor
Matthew J. Trainor, MD Department of Neurosurgery
University of Miami Hospital
Assistant Professor of Medicine
Jackson Memorial Hospital
Department of Medicine
Miami, FL
University of Massachusetts Medical School
UMass Memorial Medical Center
Worcester, MA Richard Y. Wang, DO
Senior Medical Officer
Arthur L. Trask, MD, FACS Division Laboratory Sciences
Adjunct Professor of Surgery National Center for Environmental Health
Department of Surgery Centers for Disease Control and Prevention
Uniformed Services University for Health Sciences Atlanta, GA
Springfield, MO
Wahid Y. Wassef, MD, MPH
Todd W. Trask, MD Director of Endoscopy
Director, Neurosurgery Intensive Care Unit UMass Memorial Medical Center
Department of Neurosurgery Associate Professor of Clinical Medicine
Methodist Neurological Institute University of Massachusetts Medical School
Houston, TX Department of Medicine
Division of Gastroenterology
Christoph Troppmann, MD, FACS UMass Memorial Medical Center
Professor of Surgery Worcester, MA
Department of Surgery
University of California Paul M. Wax, MD, FACMT
Davis Medical Center Clinical Professor of Surgery (Emergency Medicine)
Sacramento, CA University of Texas, Southwestern
Paradise Valley, AZ
Patrick Troy, MD Toxicology
Fellow University of Texas
Department of Pulmonary, Critical Care and Dallas, TX
Sleep Medicine
Beth Israel Deaconess Medical Center John P. Weaver, MD
Boston, MA
Associate Professor
University of Massachusetts Medical School
Cynthia B. Umali, MD (DECEASED) Department of Surgery
Department of Radiology Division of Neurosurgery
UMass Memorial Medical Center UMass Memorial Medical Center
Worcester, MA Worcester, MA
Gaurav A. Upadhyay, MD
Cardiac Fellow Mireya Wessolossky, MD
Division of Cardiology Assistant Professor
Massachusetts General Hospital Department of Medicine/Infectious Diseases
Boston, MA UMass Memorial Medical Center
Worcester, MA
Craigan T. Usher, MD
Clinical Fellow in Psychiatry Matthew J. Wieduwilt, MD, PhD
Harvard Medical School Clinical Fellow
Massachusetts General Hospital/McLean Hospital Division of Hematology and Oncology
Child & Adolescent University of California, San Francisco Medical
Psychiatry Fellow Center
Boston, MA San Francisco, CA
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Contributors xxv

Christopher H. Wigfield, MD, FRCS Rebecca J. Zapatochny Rufo, DNSc, RN, CCRN
Assistant Professor, Cardiothoracic Surgery Resurrection eICUr Program Operations Director
Department of Thoracic and Cardiovascular Surgery Department of eICU
Loyola University Medical Center Resurrection Healthcare
Maywood, IL Holy Family Medical
Des Plaines, IL
Mark M. Wilson, MD
Associate Director of Medical ICU John K. Zawacki, MD
Associate Professor Professor of Medicine
Department of Medicine Department of Medicine
Division of Pulmonary, Allergy and Critical Care Division of Gastroenterology
Medicine University of Massachusetts Medical School
University of Massachusetts Medical School UMass Memorial Medical Center
UMass Memorial Medical Center Worcester, MA
Worcester, MA
Chad A. Zender, MD, FACS
Ann E. Woolfrey, MD Assistant Professor
Associate Professor Department of Otolaryngology
Department of Clinical Research University Hospitals Case Western Reserve
Fred Hutchinson Cancer Research Center Cleveland, OH
Seattle, WA
Iva Zivna, MD
Shan Yin, MD, MPH Assistant Professor
Fellow, Medical Toxicology Department of Infectious Disease
Rocky Mountain Poison and Drug Center University of Massachusetts Medical School
Denver Health UMass Memorial Medical Center
Denver, CO Worcester, MA

Luke Yip, MD Gary R. Zuckerman, DO


US Food and Drug Administration, CDER Associate Professor of Medicine
Division of Anesthesia, Analgesia, and Addiction Products Division of Gastroenterology
Silver Spring, MD Department of Internal Medicine
Denver Health and Hospital Authority Barnes-Jewish Hospital
Department of Medicine, Medical Toxicology Washington University School of Medicine
Rocky Mountain Poison & Drug Center St. Louis, MO
Denver, CO
Marc S. Zumberg, MD, FACS
Firas E. Zahr, MD Associate Professor of Medicine
Cardiovascular Fellow Department of Medicine
Department of Cardiovascular Medicine Division of Hematology/Oncology
University of Pittsburgh Medical Center Slands Hospital/University of Florida
Pittsburgh, PA Gainesville, FL
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P R E FA C E

It is with great pleasure that we present the seventh edition (ii) decreasing variability by following clinical practice guide-
of Irwin and Rippes Intensive Care Medicine. As with pre- lines based upon the best available evidence to ensure better
vious editions, the editorial challenge that we faced with the outcomes for our patients; and (iii) doing more with less to
seventh edition was to continue to ensure that the textbook decrease the cost of caring for our patients. While these prin-
evolved as the field has evolved and improved to meet the var- ciples have always been espoused, it has become clear that we
ied and rigorous demands placed on it by the diverse group of must more consistently follow them. With respect to specific
specialty physicians and nonphysicians practicing in the adult issues, the day-to-day use of ultrasonography by critical care
intensive care environment without losing strengths that have specialists is a very recent change and this is reflected in the
made previous editions so useful and popular. We hope and liberal use of ultrasonographic images throughout the book
believe that the seventh edition of Irwin and Rippes Intensive and a new chapter entitled Interventional Ultrasound; these are
Care Medicine has risen to meet these challenges. prominently featured in the procedure and monitoring chap-
Over the past 27 years since the publication of the first ters. Moreover, there is an imperative to increasingly utilize
edition of our textbook, dramatic changes have occurred in information technology in the everyday practice of intensive
virtually every area of critical care, and these are reflected in care medicine. This not only includes using electronic medical
the evolution of our textbook. While our textbook initially records, computer physician order entry, and clinical decision
focused primarily on medical intensive care, it now provides support tools but also tele-ICU. All of these issues are covered
an interdisciplinary emphasis on anesthesia, surgery, trauma, in the section entitled Contemporary Challenges in the Inten-
and neurointensive care as well as medical intensive care with sive Care Unit edited by Craig Lilly.
strong collaboration across all these disciplines. With this edi- In coronary care, rapid advances in techniques and inter-
tion, a critical care nursing-centric section has been added. This ventions continue to occur. These changes are reflected in the
reflects the reality that intensive care medicine has inevitably Cardiovascular Problems and Coronary Care section of the
become more interdisciplinary and collaborative. seventh edition. It is interesting to see how cardiovascular in-
The seventh edition is approximately the same length as the tensive care has dramatically changed since the publication of
previous edition. To make this happen, we challenged every our first few editions, as the advances in cardiology and cardiac
section editor and author to carefully balance edited materi- surgery became known from the large, multicenter, randomized
als emphasizing new evidence-based as well as state-of-the-art controlled clinical trials. We welcome Akshay Desai who has
information by discarding outdated information. All of our joined Patrick OGara as co-section editor for this section.
section editors and chapter authors have done a superb job Equally important advances have occurred in surgical criti-
meeting this challenge. All chapters in every section have been cal care, including new therapies and techniques in a variety of
updated with recent references and other materials that reflect conditions treated in this environment. Our Surgical Problems
current information, techniques, and principles. New chapters in the Intensive Care Unit section remains a great strength
have been added to reflect emerging areas of interest. As stated of this book. Fred Luchette did his usual magnificent job on
earlier, an entirely new section has been added on Nursing this edition. We recognize Arthur Trask and Stephen Barnes
Issues in the ICU that was ably coedited by Dorrie Fontaine who have done an admirable job of updating the Shock and
and Shawn Cody. This section was meant to focus on issues Trauma section of the textbook as well.
related to collaboration, healthy work environments, and the While our textbook has been updated and broadened to
expanding roles of nurses not the specifics of nursing care that include new understandings, information and techniques, our
have been brilliantly covered in textbooks of ICU nursing; and goal has been to maintain the practical, clinically oriented ap-
Dorrie and Shawn have admirably succeeded in this regard. An- proach that readers have come to expect from previous edi-
other new section on Critical Care Consequences of Weapons tions. Our editorial focus remains on clinically relevant studies
(or Agents) of Mass Destruction reflects the changing realities and information that readers have found so useful in the pre-
of our world and has been ably edited by Larry Mohr. vious six editions.
Evidenced-based medicine continues to play an ever more As in the past, our textbook opens with a detailed section
prominent role in all branches of medicine including critical on commonly performed Procedures and Techniques in the
care. With this in mind, we have asked every chapter author Intensive Care Unit. This section, along with the Mini-
to make recommendations that specifically reflect recent trials mally Invasive Monitoring section, has also been simultane-
with a particular emphasis on randomized prospective con- ously published as a smaller book entitled Procedures, Tech-
trolled trials. Authors have summarized such evidence, when niques, and Minimally Invasive Monitoring in Intensive Care
the data have allowed, with helpful tables. Medicine. All chapters in these sections have been updated with
In medical intensive care, important changes and advances new figures and descriptions of techniques which have been
have occurred since the publication of the sixth edition. These added to reflect changes since the sixth edition of the textbook.
include managing our ICUs according to the following guid- We are indebted that section editors Stephen Heard and Alan
ing principles: (i) making our ICUs safer for our patients; Lisbon who have done a superb job on these sections.

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xxviii Preface

The Pharmacology, Overdoses, and Poisoning section, Some new section editors have joined us for the seventh
consisting of 29 chapters, remains a great strength of this book edition and done great work. In addition to the individuals
and essentially represents a textbook on these topics embedded that we have already mentioned, we would like to specifically
into our larger book. In this edition, we welcome new section acknowledge the excellent efforts by the following new sec-
editors Luke Yip and Kennon Heard who have joined Steven tion editors or co-section editors: Pang-Yen Fan (Renal), Do-
Bird as section editors for this outstanding and comprehensive minic Nompleggi (Gastrointestinal Problems), Patrick Fogarty
section. (Hematologic Problems), David Paydarfar (Neurologic Prob-
Because intensive care cannot be divorced from public pol- lems), David Harlan (Endocrine Problems), and Nancy Liu
icy, we continue to emphasize this with a major section of our (Rheumatologic, Immunologic and Dermatologic Problems).
textbook entitled Contemporary Challenges in the Intensive As with previous editions, our emphasis remains on clinical
Care Unit. This section includes not only more ethical and management. Discussions of basic pathophysiology are also in-
legal issues but also issues related to ICU organization and cluded and guided and supplemented by extensive references
management, economics, safety, and information technology. to help clinicians and researchers who wish to pursue more
With this edition, we welcome Craig Lilly, who has done an in-depth knowledge of these important areas. When therapies
outstanding job on this section. reflect institutional or individual bias or are considered contro-
Our team of section editors continue to do a wonderful versial, we have attempted to indicate this.
job coordinating large bodies of information that comprise We hope and believe that the outstanding efforts of many
the core of modern intensive care. Many of our section editors people over the past 4 years have continued to result in an
have been with us for one or more editions. Richard Ellison III evidence-based and state-of-the-art and comprehensive text-
(Infectious Disease), Neil Aronin (Endocrinology), Stephanie book that will elucidate the important principles in intensive
Levine (Transplantation), Dominic Nompleggi (Metabolism/ care and will continue to guide and support the best efforts of
Nutrition), Mark Madison (Pulmonary), John Querques practitioners in this challenging environment in their ongoing
(Psychiatry), and Joseph Frassica (Appendix, Calculations efforts to diagnosis and treat complicated diseases and relieve
Commonly used in Critical Care) all fall into this category and human suffering.
have done their usual, excellent job. A new table on Antidotes
has been added to the Appendix based on the efforts of Luke Richard S. Irwin, MD, Master FCCP
Yip, Jeremy Helphenstine, Jerry Thomas, and Ian Ball. James M. Rippe, MD
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ACKNOWLEDGMENTS

Numerous outstanding individuals have made significant con- this textbook. We have very much appreciated their deep com-
tributions to all phases of writing and production of this text- mitment to this book and to advancing the field of intensive
book and deserve special recognition and thanks. First and care medicine.
foremost is our managing editor, Elizabeth Grady. Beth lit- Our editors at Lippincott Williams & Wilkins including
erally lives and breathes this textbook as it works its way Brian Brown, executive editor, have been a source of great help
through the production cycle every 4 years. She is the guid- and encouragement. As with the last edition, Nicole Dernoski
ing and organizing force behind this textbook. It would sim- continues to be extremely helpful and accommodating in su-
ply not be possible without Beths incredible organizational pervising and coordinating all phases of production in an out-
skills, good humor, and enormous energy. She has guided this standing way.
book through six editionsthis book is as much hers as it is Lastly, we are grateful to Indu Jawwad and her staff for the
ours. outstanding job they have done copyediting the manuscript for
Our administrative assistants, office assistant, and clinical this edition.
coordinators, Carol Moreau, Debra Adamonis, Karen Barrell, Our families support our efforts with unfailing encourage-
Mary Garabedian, and Cynthia French have helped us con- ment and love. To them, and the many others who have helped
tinue to coordinate and manage our complex professional and in ways too numerous to count, we are deeply grateful.
personal lives and create room for the substantial amount of
time required to write and edit. Our section editors have de- Richard S. Irwin, MD, Master FCCP
voted enormous skill, time, and resources to every edition of James M. Rippe, MD

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CONTENTS

Contributors v
Preface xxvii
Acknowledgments xxix

S E C T I O N I P R O C E D U R E S, T E C H N I Q U E S, AND
M I N I M A L LY I N VA S I V E M O N I T O R I N G

Chapter 1 Airway Management and Endotracheal Intubation 1


J. Matthias Walz, Shubjeet Kaur and Stephen O. Heard
Chapter 2 Central Venous Catheters 16
Jason Lee-Llacer and Michael G. Seneff
Chapter 3 Arterial Line Placement and Care 36
Jason Lee-Llacer and Michael G. Seneff
Chapter 4 Pulmonary Artery Catheters 45
Harvey S. Reich
Chapter 5 Temporary Cardiac Pacing 64
Seth T. Dahlberg
Chapter 6 Cardioversion and Defibrillation 71
Mark S. Link and Naomi F. Botkin
Chapter 7 Pericardiocentesis 77
Craig S. Smith and Richard C. Becker
Chapter 8 Chest Tube Insertion and Care 83
Ulises Torres and Robert A. Lancy
Chapter 9 Bronchoscopy 89
Stephen J. Krinzman, Paulo J. Oliveira and Richard S. Irwin
Chapter 10 Thoracentesis 95
Mark M. Wilson and Richard S. Irwin
Chapter 11 Arterial Puncture for Blood Gas Analysis 102
Kimberly A. Robinson and Richard S. Irwin
Chapter 12 Tracheostomy 105
Scott E. Kopec and Timothy A. Emhoff
Chapter 13 Gastrointestinal Endoscopy 116
Anupam Singh, Randall S. Pellish and Wahid Y. Wassef
Chapter 14 Paracentesis and Diagnostic Peritoneal Lavage 122
Lena M. Napolitano
Chapter 15 Gastroesophageal Balloon Tamponade for Acute Variceal
Hemorrhage 130
Marie T. Pavini and Juan Carlos Puyana

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xxxii Contents

Chapter 16 Endoscopic Placement of Feeding Tubes 136


Lena M. Napolitano
Chapter 17 Cerebrospinal Fluid Aspiration 143
John P. Weaver
Chapter 18 Percutaneous Suprapubic Cystostomy 150
Satya Allaparthi, K.C. Balaji and Philip J. Ayvazian
Chapter 19 Aspiration of the Knee and Synovial Fluid Analysis 155
Bonnie J. Bidinger and Eric W. Jacobson
Chapter 20 Anesthesia for Bedside Procedures 160
Mark Dershwitz
Chapter 21 Interventional Ultrasound 168
Gisela I. Banauch and Paul H. Mayo
Chapter 22 Interventional Radiology: Percutaneous Drainage
Techniques 175
Brian T. Callahan, Salomao Faintuch and Felipe B. Collares
Chapter 23 Cardiopulmonary Resuscitation 181
Bruce Greenberg and John A. Paraskos
Chapter 24 Management of Pain in the Critically Ill Patient 206
Armagan Dagal, Mario De Pinto and W. Thomas Edwards
Chapter 25 Therapeutic Paralysis 219
Khaldoun Faris

S E C T I O N I I M I N I M A L LY I N VA S I V E M O N I T O R I N G

Chapter 26 Routine Monitoring of Critically Ill Patients 227


Patrick Troy, Nicholas A. Smyrnios and Michael D. Howell

Chapter 27 Minimally Invasive Hemodynamic Monitoring 245


Andrew J. Goodwin, Ednan K. Bajwa and Atul Malhotra

Chapter 28 Neurologic Multimodal Monitoring 258


Raphael A. Carandang, Wiley R. Hall and Donald S. Prough
Chapter 29 Echocardiography in the Intensive Care Unit 271
Achikam Oren-Grinberg, Sajid Shahul and Adam B. Lerner
Chapter 30 Monitoring Gastrointestinal Tract Function 286
Ruben J. Azocar, Laura Santos Pavia and Suresh Agarwal

Chapter 31 Respiratory Monitoring during Mechanical Ventilation 294


Todd W. Sarge, Ray Ritz and Daniel Talmor

S E C T I O N I I I C A R D I O VA S C U L A R PROBLEMS AND
CORONARY CARE

Chapter 32 Approach to the Patient with Hypotension and


Hemodynamic Instability 307
Michael M. Givertz and James C. Fang
Chapter 33 Management of Advanced Heart Failure 318
G. William Dec
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Contents xxxiii

Chapter 34 Valvular Heart Disease 328


Garrick C. Stewart and Patrick T. OGara
Chapter 35 Critical Care of Pericardial Disease 347
Akshay S. Desai and Kenneth L. Baughman
Chapter 36 Acute Aortic Syndromes 358
Leon M. Ptaszek, Eric M. Isselbacher and Amy E. Spooner
Chapter 37 Evaluation and Management of Hypertension in the
Intensive Care Unit 373
Benjamin M. Scirica and Robert J. Heyka

Chapter 38 Unstable Angina/NonST-Segment Elevation


Myocardial Infarction 382
Suzanne J. Baron, Christopher P. Cannon and Marc S. Sabatine
Chapter 39 ST-Segment Elevation Myocardial Infarction 402
James A. de Lemos and David A. Morrow
Chapter 40 Mechanical Complications of Myocardial Infarction 419
Annabel A. Chen-Tournoux and Michael A. Fifer
Chapter 41 Ventricular Tachycardia 428
Melanie Maytin and Bruce A. Koplan

Chapter 42 Supraventricular Tachycardias: Recognition and


Management in the Intensive Care Setting 441
Ammar Habib, Joseph J. Gard, Traci L. Buescher and
Samuel J. Asirvatham

Chapter 43 Bradyarrhythmias and Temporary Pacing 455


Gaurav A. Upadhyay and Jagmeet P. Singh

Chapter 44 How to Manage Cardiac Pacemakers and Implantable


Defibrillators in the Intensive Care Unit 466
Melanie Maytin and Usha B. Tedrow
Chapter 45 Mechanical Support for Heart Failure 477
Jeffrey J. Teuteberg and Firas E. Zahr

SECTION IV PULMONARY PROBLEMS IN THE


INTENSIVE CARE UNIT

Chapter 46 Respiratory Failure Part I: A Physiologic Approach to


Respiratory Failure 488
Thaddeus C. Bartter, Melvin R. Pratter, Wissam Abouzgheib and
Richard S. Irwin

Chapter 47 Respiratory Failure Part II: Acute Respiratory Distress


Syndrome 493
Gilman B. Allen and Polly E. Parsons

Chapter 48 Respiratory Failure Part III: Asthma 512


J. Mark Madison and Richard S. Irwin

Chapter 49 Respiratory Failure Part IV: Chronic Obstructive


Pulmonary Disease 525
Meyer S. Balter and Ronald F. Grossman
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xxxiv Contents

Chapter 50 Respiratory Failure Part V: Extrapulmonary Causes of


Respiratory Failure 534
Helen M. Hollingsworth, Melvin R. Pratter and Richard S. Irwin

Chapter 51 Respiratory Failure Part VI: Acute Respiratory Failure


in Pregnancy 548
Christine Campbell-Reardon and Helen M. Hollingsworth
Chapter 52 Venous Thromboembolism: Pulmonary Embolism and
Deep Venous Thrombosis 565
Charles William Hargett, III and Victor F. Tapson
Chapter 53 Managing Hemoptysis 578
Richard S. Irwin and Kimberly A. Robinson
Chapter 54 Aspiration 587
Kimberly A. Robinson and Richard S. Irwin

Chapter 55 Drowning 594


Nicholas A. Smyrnios and Richard S. Irwin
Chapter 56 Pulmonary Hypertension in the Intensive Care Unit 601
Kimberly A. Fisher and Harrison W. Farber
Chapter 57 Pleural Disease in the Critically Ill Patient 608
Peter Doelken and Steven A. Sahn
Chapter 58 Mechanical Ventilation Part I: Invasive 624
Richard A. Oeckler, Rolf D. Hubmayr and Richard S. Irwin
Chapter 59 Mechanical Ventilation Part II: Non-invasive Mechanical
Ventilation for the Adult Hospitalized Patient 641
Samy S. Sidhom and Nicholas Hill

Chapter 60 Mechanical Ventilation Part III: Discontinuation 658


Richard S. Irwin, Nicholas A. Smyrnios and Rolf D. Hubmayr

Chapter 61 Gas Embolism Syndromes: Venous Gas Emboli, Arterial


Gas Emboli, and Decompression Sickness 669
Mark M. Wilson
Chapter 62 Respiratory Adjunct Therapy 684
Scott E. Kopec and Richard S. Irwin

Chapter 63 Chest Radiographic Examination 700


Cynthia B. Umali and Jerry P. Balikian
Chapter 64 Acute Inhalation Injury 731
David J. Prezant, Dorsett D. Smith and Lawrence C. Mohr Jr
Chapter 65 Disorders of Temperature Control Part I: Hypothermia 745
M. Kathryn Steiner, Frederick J. Curley and Richard S. Irwin

Chapter 66 Disorders of Temperature Control Part II: Hyperthermia 761


M. Kathryn Steiner, Frederick J. Curley and Richard S. Irwin
Chapter 67 Severe Upper Airway Infections 776
Stephen J. Krinzman, Sunil Rajan and Richard S. Irwin
Chapter 68 Acute Infectious Pneumonia 791
Veronica Brito and Michael S. Niederman
Chapter 69 Lung Biopsy 815
Scott E. Kopec and Richard S. Irwin

Chapter 70 Sleep Issues in the Intensive Care Unit Setting 823


Kim L. Goring and Nancy A. Collop
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SECTION V RENAL PROBLEMS IN THE


INTENSIVE CARE UNIT

Chapter 71 Metabolic Acidosis and Metabolic Alkalosis 831


Robert M. Black

Chapter 72 Disorders of Plasma Sodium and Plasma Potassium 843


Robert M. Black
Chapter 73 Acute Kidney Injury in the Intensive Care Unit 867
Jahan Montague and Konstantin Abramov
Chapter 74 Drug Dosing in Renal and Hepatic Failure:
A Pharmacokinetic Approach to the Critically Ill Patient 893
Sonia Lin, Keith J. Foster, Ronald J. DeBellis and Brian S. Smith
Chapter 75 Renal Replacement Therapy in the Intensive Care Unit 917
Glenn Kershaw, Matthew J. Trainor and Pang-Yen Fan

SECTION VI INFECTIOUS DISEASE PROBLEMS IN THE


INTENSIVE CARE UNIT

Chapter 76 Approach to Fever in the ICU Patient 932


Raul E. Davaro and Richard H. Glew
Chapter 77 Use of Antimicrobials in the Treatment of Infection in the
Critically Ill Patient 939
Iva Zivna, Richard H. Glew and Jennifer S. Daly

Chapter 78 Prevention and Control of Healthcare-Acquired Infections


in the Intensive Care Unit 952
Mireya Wessolossky and Richard T. Ellison, III

Chapter 79 Central Nervous System Infections 959


Heidi L. Smith and Alan L. Rothman
Chapter 80 Infective Endocarditis and Infections of Intracardiac
Prosthetic Devices 969
Karen C. Carroll, Sarah H. Cheeseman and Sara E. Cosgrove
Chapter 81 Infections Associated with Vascular Catheters 986
Suzanne F. Bradley and Carol A. Kauffman
Chapter 82 Urinary Tract Infections 994
Steven M. Opal
Chapter 83 Life-Threatening Community-Acquired Infections:
Toxic Shock Syndrome, Overwhelming Postsplenectomy
Infection, Meningococcemia, Malaria, Rocky Mountain
Spotted Fever, and Others 1004
Mary T. Bessesen
Chapter 84 Acute Infection in the Immunocompromised Host 1014
Jennifer S. Daly and Robert W. Finberg
Chapter 85 Intensive Care of Patients with HIV Infection 1023
Sarah H. Cheeseman and Mark J. Rosen

Chapter 86 Infectious Complications of Drug Abuse 1030


Afroza Liton and William L. Marshall
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Chapter 87 Tuberculosis 1036


Robert W. Belknap and Randall R. Reves
Chapter 88 Botulism 1044
Mary Dawn T. Co and Richard T. Ellison, III
Chapter 89 Tetanus 1046
Mary Dawn T. Co and Richard T. Ellison, III
Chapter 90 Serious Epidemic Viral Pneumonias 1049
Daniel H. Libraty

SECTION VII GASTROINTESTINAL DISEASE PROBLEMS


IN THE INTENSIVE CARE UNIT

Chapter 91 Upper and Lower Gastrointestinal Bleeding 1059


Ryan F. Porter, Gary R. Zuckerman and
Chandra Prakash Gyawali
Chapter 92 Stress Ulcer Syndrome 1067
Sonal Kumar, Chandra Prakash Gyawali and Gary R. Zuckerman
Chapter 93 Gastrointestinal Motility in the Critically Ill Patient 1072
Filippo Cremonini, Anthony J. Lembo, Brennan M.R. Spiegel and
Inder M. Singh
Chapter 94 Fulminant Colitis and Toxic Megacolon 1079
Stephen B. Hanauer
Chapter 95 Evaluation and Management of Liver Failure 1083
Gowri Kularatna and Mauricio Lisker-Melman
Chapter 96 Diarrhea 1095
Colin T. Swales, Laura Harrell, Eugene Chang and John K. Zawacki
Chapter 97 Severe and Complicated Biliary Tract Disease 1103
John M. Iskander, Sreenivasa S. Jonnalagadda and Riad Azar
Chapter 98 Hepatic Dysfunction 1108
Mauricio Lisker-Melman and Gowri Kularatna

Chapter 99 Acute Pancreatitis 1115


Michael L. Steer

SECTION VIII ENDOCRINE PROBLEMS IN THE


INTENSIVE CARE UNIT

Chapter 100 Management of Hyperglycemia in Critically Ill Patients 1130


Michael J. Thompson, David M. Harlan, Samir Malkani and
John P. Mordes

Chapter 101 Hyperglycemic Diabetic Coma 1139


Samir Malkani, Aldo A. Rossini, David M. Harlan,
Michael J. Thompson and John P. Mordes

Chapter 102 Severe Hyperthyroidism 1151


Marjorie S. Safran
Chapter 103 Myxedema Coma 1155
Mira Sofia Torres and Charles H. Emerson
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Chapter 104 Hypoadrenal Crisis and the Stress Management of the


Patient on Chronic Steroid Therapy 1159
Neil Aronin

Chapter 105 Disorders of Mineral Metabolism 1162


Seth M. Arum and Daniel T. Baran

Chapter 106 Hypoglycemia 1168


John P. Mordes, Michael J. Thompson, David M. Harlan
and Samir Malkani

Chapter 107 Nonthyroidal Illness Syndrome (Sick Euthyroid Syndrome)


in the Intensive Care Unit 1182
Shirin Haddady and Alan P. Farwell

SECTION IX HEMATOLOGIC AND ONCOLOGIC


PROBLEMS IN THE INTENSIVE CARE UNIT

Chapter 108 Disorders of Hemostasis in Critically Ill Patients 1195


Jeremiah Boles and Alice D. Ma

Chapter 109 Thrombocytopenia 1211


Thomas G. DeLoughery
Chapter 110 Antithrombotic Pharmacotherapy 1224
Christopher D. Adams, Kevin E. Anger, Bonnie C. Greenwood and
John Fanikos

Chapter 111 Diagnosis and Management of Prothrombotic Disorders in


the Intensive Care Unit 1243
Ashkan Emadi and Michael B. Streiff

Chapter 112 Anemia in the Critical Care Setting 1253


Marc S. Zumberg, Marc J. Kahn and Alice D. Ma

Chapter 113 Therapeutic Apheresis: Technical Considerations and


Indications in Critical Care 1267
Theresa A. Nester and Michael Linenberger
Chapter 114 Transfusion Therapy: Blood Components and Transfusion
Complications 1276
Terry Gernsheimer
Chapter 115 Critical Care of Patients with Hematologic Malignancies 1284
Matthew J. Wieduwilt and Lloyd E. Damon
Chapter 116 Oncologic Emergencies 1296
Damian J. Green, John A. Thompson and Bruce Montgomery

S E C T I O N X P H A R M A C O L O G Y, O V E R D O S E S,
AND POISONINGS

Chapter 117 General Considerations in the Evaluation and Treatment of


Poisoning 1309
Ian M. Ball and Christopher H. Linden

Chapter 118 Acetaminophen Poisoning 1329


Steven B. Bird
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Chapter 119 Alcohols and Glycol Poisoning 1337


Jennifer L. Englund, Marco L.A. Sivilotti and Marsha D. Ford
Chapter 120 Antiarrhythmic Agents 1353
Michael Ganetsky
Chapter 121 Anticholinergic Poisoning 1363
Keith K. Burkhart
Chapter 122 Anticonvulsant Poisoning 1366
Steven B. Bird
Chapter 123 Antidepressant Poisoning 1376
Cynthia K. Aaron and Abhishek Katiyar
Chapter 124 Antipsychotic Poisoning 1386
Michael J. Burns and Christopher H. Linden
Chapter 125 Beta-Blocker Poisoning 1397
Shan Yin and Javier C. Waksman
Chapter 126 Calcium Channel Antagonist Poisoning 1403
Christopher R. DeWitt

Chapter 127 Cardiac Glycoside Poisoning 1409


Mark A. Kirk and Bryan S. Judge
Chapter 128 Cholinergic Poisoning 1413
Cynthia K. Aaron

Chapter 129 Cocaine Poisoning 1418


Richard D. Shih and Judd E. Hollander
Chapter 130 Corrosive Poisoning 1423
Robert P. Dowsett and Christopher H. Linden
Chapter 131 Salicylate and Other Nonsteroidal Anti-Inflammatory
Drug Poisoning 1430
Marco L.A. Sivilotti and Christopher H. Linden

Chapter 132 Envenomations 1439


Robert L. Norris
Chapter 133 Heavy Metal Poisoning 1449
Luke Yip
Chapter 134 Hydrocarbon Poisoning 1464
William J. Lewander and Alfred Aleguas Jr
Chapter 135 Hydrofluoric Acid Poisoning 1471
Kennon Heard
Chapter 136 Iron Poisoning 1473
Milton Tenenbein

Chapter 137 Isoniazid Poisoning 1478


James B. Mowry and R. Brent Furbee

Chapter 138 Lithium Poisoning 1481


Kent R. Olson and Thanjira Jiranantakan
Chapter 139 Methylxanthine Poisoning 1486
Michael W. Shannon
Chapter 140 Opioid Poisoning 1492
Robert P. Dowsett and Luke Yip
Chapter 141 Pesticide Poisoning 1499
William K. Chiang and Richard Y. Wang
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Chapter 142 Phencyclidine and Hallucinogen Poisoning 1516


Frank F. Daly and Luke Yip
Chapter 143 SedativeHypnotic Agent Poisoning 1521
Andis Graudins
Chapter 144 Amphetamines 1529
Michael C. Beuhler
Chapter 145 Withdrawal Syndromes 1536
Paul M. Wax and Jennifer Smith

SECTION XI SURGICAL PROBLEMS IN THE


INTENSIVE CARE UNIT

Chapter 146 Epistaxis 1548


Avinash V. Mantravadi, Chad A. Zender and Louis G. Portugal
Chapter 147 Esophageal Perforation and Acute Mediastinitis 1555
Jason W. Smith, Christopher H. Wigfield and Robert B. Love

Chapter 148 Management of the Postoperative Cardiac Surgical Patient 1562


Sajid Shahul, Cathy Dudick and Alan Lisbon
Chapter 149 Noncardiac Surgery in the Cardiac Patient 1575
Steven B. Edelstein and Scott W. Byram

Chapter 150 Diagnosis and Management of Intra-abdominal Sepsis 1591


Dennis I. Sonnier, Shrawan G. Gaitonde, Patrick D. Solan and
Thomas L. Husted

Chapter 151 Mesenteric Ischemia 1605


Takki Momin and John Ricotta
Chapter 152 Compartment Syndrome of the Abdominal Cavity 1612
Ajai K. Malhotra and Rao R. Ivatury

Chapter 153 Necrotizing Soft Tissue Infections 1619


Richard L. Gamelli and Joseph A. Posluszny Jr

Chapter 154 Acute Limb Ischemia: Etiology, Diagnosis, and Treatment


Strategies 1626
Pegge M. Halandras and Ross Milner
Chapter 155 Pressure Sores: Prevention and Treatment 1630
Victor G. Cimino, Wellington J. Davis III and Samir R. Shah
Chapter 156 Management of the Obstetrical Patient in the Intensive
Care Setting 1636
John G. Gianopoulos and Jonathan F. Critchlow

SECTION XII SHOCK AND TRAUMA

Chapter 157 Shock: An Overview 1644


Michael L. Cheatham, Ernest F.J. Block, Howard G. Smith,
Matthew W. Lube and John T. Promes

Chapter 158 Resuscitation from Shock Following Injury 1656


Donald H. Jenkins, John B. Holcomb, Phillip A. Letourneau,
Dustin L. Smoot and Stephen L. Barnes
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Chapter 159 The Management of Sepsis 1669


Paul E. Marik
Chapter 160 Multiple Organ Dysfunction Syndrome 1679
Andrew C. Bernard and Timothy A. Pritts
Chapter 161 Trauma Systems 1684
Christoph R. Kaufmann and Kevin Dwyer
Chapter 162 Traumatic Brain Injury 1687
Todd W. Trask and Arthur L. Trask
Chapter 163 Spinal Cord Trauma 1691
Howard B. Levene, Michael Y. Wang and Barth A. Green
Chapter 164 Thoracic and Cardiac Trauma 1704
Scott B. Johnson and John G. Myers
Chapter 165 Critical Care of the Patient with Abdominal Trauma 1717
Justin L. Regner and John B. Cone
Chapter 166 Burn Management 1727
Philip Fidler

Chapter 167 Orthopedic Injury 1733


Gregory J. Della Rocca and Sean E. Nork

SECTION XIII NEUROLOGIC PROBLEMS IN THE


INTENSIVE CARE UNIT

Chapter 168 An Approach to Neurologic Problems in the Intensive


Care Unit 1747
David A. Drachman
Chapter 169 Evaluating the Patient with Altered Consciousness in the
Intensive Care Unit 1750
Raphael A. Carandang, Lawrence J. Hayward and
David A. Drachman

Chapter 170 Metabolic Encephalopathy 1760


Paula D. Ravin

Chapter 171 Generalized Anoxia/Ischemia of the Nervous System 1768


Carol F. Lippa and Majaz Moonis
Chapter 172 Status Epilepticus 1772
Jaishree Narayanan and Catherine A. Phillips
Chapter 173 Cerebrovascular Disease 1778
Majaz Moonis, John P. Weaver and Marc Fisher

Chapter 174 Neuro-Oncological Problems in the Intensive Care Unit 1787


N. Scott Litofsky and Michael C. Muzinich

Chapter 175 GuillainBarre Syndrome 1797


Isabelita R. Bella and David A. Chad
Chapter 176 Myasthenia Gravis in the Intensive Care Unit 1805
Isabelita R. Bella and Randall R. Long
Chapter 177 Miscellaneous Neurologic Problems in the Intensive
Care Unit 1811
Jing Ji, Ann L. Mitchell and Nancy M. Fontneau
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Chapter 178 Subarachnoid Hemorrhage 1819


Wiley R. Hall, Majaz Moonis and John P. Weaver
Chapter 179 Mental Status Dysfunction in the Intensive Care Unit:
Postoperative Cognitive Impairment 1826
Joan M. Swearer and Shashidhara Nanjundaswamy

Chapter 180 Newly Acquired Weakness in the Intensive Care Unit:


Critical Illness Myopathy and Neuropathy 1829
David A. Chad

SECTION XIV TRANSPLANTATION

Chapter 181 Immunosuppression in Solid-Organ Transplantation 1833


Amit Basu, Arthur J. Matas and Abhinav Humar
Chapter 182 Critical Care Problems in Kidney Transplant Recipients 1846
Mark L. Sturdevant and Rainer W.G. Gruessner
Chapter 183 Specific Critical Care Problems in Heart and Heart-Lung
Transplant Recipients 1857
Sara J. Shumway and Eias E. Jweied
Chapter 184 Care of the Pancreas Transplant Recipient 1866
Robert M. Esterl Jr, Gregory A. Abrahamian,
David E.R. Sutherland and Raja Kandaswamy

Chapter 185 Management of the Organ Donor 1879


Christoph Troppmann
Chapter 186 Diagnosis and Management of Rejection, Infection, and
Malignancy in Transplant Recipients 1903
Tun Jie, David L. Dunn and Rainer W.G. Gruessner
Chapter 187 Critical Care of the Liver and Intestinal Transplant
Recipients 1920
Ruy J. Cruz Jr, William D. Payne and Abhinav Humar

Chapter 188 Hematopoietic Cell Transplantation 1938


Paul A. Carpenter, Marco Mielcarek and Ann E. Woolfrey

Chapter 189 Critical Care of the Lung Transplant Recipient 1957


Luis F. Angel and Stephanie M. Levine

SECTION XV METABOLISM/NUTRITION

Chapter 190 Nutritional Therapy in the Critically Ill Patient 1969


Dominic J. Nompleggi
Chapter 191 Parenteral and Enteral Nutrition in the Intensive
Care Unit 1974
David F. Driscoll and Bruce R. Bistrian
Chapter 192 Disease-Specific Nutrition 1990
Mickey M. Ott, Bryan R. Collier and Douglas Seidner
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SECTION XVI RHEUMATOLOGIC, IMMUNOLOGIC, AND


DERMATOLOGIC PROBLEMS IN THE INTENSIVE CARE UNIT

Chapter 193 Rheumatologic Diseases in the Intensive Care Unit 2004


Nancy Y.N. Liu and Judith A. Stebulis

Chapter 194 Anaphylaxis 2031


Frederic F. Little and Helen M. Hollingsworth
Chapter 195 Dermatology in the Intensive Care Unit 2043
Nikki A. Levin, Dori Goldberg, Lauren Alberta-Wszolek,
Megan Bernstein and Alexis C. Perkins

Chapter 196 Vasculitis in the Intensive Care Unit 2064


Paul F. Dellaripa and Donough Howard

SECTION XVII PSYCHIATRIC ISSUES IN


INTENSIVE CARE

Chapter 197 Diagnosis and Treatment of Agitation and Delirium in the


Intensive Care Unit Patient 2073
Jason P. Caplan
Chapter 198 Diagnosis and Treatment of Anxiety in the Intensive Care
Unit Patient 2080
Shelley A. Holmer and Robert M. Tighe

Chapter 199 Diagnosis and Treatment of Depression in the Intensive


Care Unit Patient 2087
Edith S. Geringer, John Querques, Meghan S. Kolodziej,
Tuesday E. Burns and Theodore A. Stern

Chapter 200 Managing the Suicidal Patient in the Intensive Care Unit 2099
Saori A. Murakami and Hoa Thi Lam
Chapter 201 Problematic Behaviors of Patients, Family, and Staff in the
Intensive Care Unit 2103
Craigan T. Usher

Chapter 202 Recognition and Management of Staff Stress in the


Intensive Care Unit 2108
Guy Maytal

SECTION XVIII NURSING

Chapter 203 Use of Nursing-Sensitive Quality Indicators 2114


Margaret Laccetti and Cheryl H. Dunnington
Chapter 204 Role of the Advanced Practice Nurse in Critical Care 2120
Theresa R. Macfarlan
Chapter 205 Interprofessional Collaboration Among Critical Care
Team Members 2123
Debra Gerardi and Dorrie K. Fontaine
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Chapter 206 Healthy Work Environments: Necessary for Providers


and Patients 2131
Kathleen M. McCauley

Chapter 207 ICU Nursing in the Telemedicine Age 2137


Rebecca J. Zapatochny Rufo, Teresa A. Rincon and Shawn Cody

SECTION XIX CONTEMPORARY CHALLENGES IN THE


INTENSIVE CARE UNIT

Chapter 208 ICU Organization and Management 2143


Thomas L. Higgins and Jay S. Steingrub
Chapter 209 Critical Care Information Systems: Structure, Function,
and Future 2152
William F. Bria, Joseph J. Frassica, Richard Kremsdorf,
M. Michael Shabot and Violet L. Shaffer

Chapter 210 Defining and Measuring Patient Safety in the Critical


Care Unit 2160
Alan M. Fein, Steven Y. Chang, Sara L. Merwin, David Ost and
John E. Heffner

Chapter 211 Medical Ethics, End of Life Care, and Clinical Research in
the Intensive Care Unit 2170
Mark Tidswell, Paul G. Jodka and Jay S. Steingrub
Chapter 212 Assessing the Value and Impact of Critical Care in an Era
of Limited Resources: Outcomes Research in the Intensive
Care Unit 2180
Andrew F. Shorr, William L. Jackson Jr and Derek C. Angus

SECTION XX CRITICAL CARE CONSEQUENCES OF


WEAPONS (OR AGENTS) OF MASS DESTRUCTION

Chapter 213 Biological Agents of Mass Destruction 2189


Angeline A. Lazarus, Asha Devereaux and Lawrence C. Mohr Jr
Chapter 214 Chemical Agents of Mass Destruction 2208
James Geiling and Lawrence C. Mohr Jr
Chapter 215 The Management of Acute Radiation Casualties 2217
Lawrence C. Mohr Jr

Chapter 216 Planning and Organization for Emergency Mass


Critical Care 2225
James Geiling, Robert M. Gougelet and Lawrence C. Mohr Jr

APPENDIX

Calculations Commonly Used in Critical Care 2232


Joseph J. Frassica

Index 2255
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SECTION I PROCEDURES, TECHNIQUES, AND


MINIMALLY INVASIVE MONITORING
STEPHEN O. HEARD

CHAPTER 1 AIRWAY MANAGEMENT AND


ENDOTRACHEAL INTUBATION
J. MATTHIAS WALZ, SHUBJEET KAUR AND STEPHEN O. HEARD

In the emergency room and critical care environment, manage- has a difficult airway and when learning how to insert airway
ment of the airway to ensure optimal ventilation and oxygena- devices such as the laryngeal mask airway (LMA; discussed in
tion is of prime importance. Although initial efforts should be Management of the Difficult Airway section).
directed toward improving oxygenation and ventilation with-
out intubating the patient (see Chapter 59) [1], these interven-
tions may fail and the placement of an endotracheal tube may Nasopharynx
be required. Although endotracheal intubation is best left to the
trained specialist, emergencies often require that the procedure The base of the skull forms the roof of the nasopharynx, and
be performed before a specialist arrives. Because intubated pa- the soft palate forms the floor. The roof and the posterior walls
tients are commonly seen in the intensive care unit (ICU) and of the nasopharynx contain lymphoid tissue (adenoids), which
coronary care unit, all physicians who work in these environ- may become enlarged and compromise nasal airflow or become
ments should be skilled in the techniques of airway manage- injured during nasal intubation, particularly in children. The
ment, endotracheal intubation, and management of intubated Eustachian tubes enter the nasopharynx on the lateral walls and
patients. may become blocked secondary to swelling during prolonged
nasotracheal intubation.

ANATOMY
Oropharynx
An understanding of the techniques of endotracheal intuba-
tion and potential complications is based on knowledge of the The soft palate defines the beginning of the oropharynx, which
anatomy of the respiratory passages [2]. Although a detailed extends inferiorly to the epiglottis. The palatine tonsils pro-
anatomic description is beyond the scope of this book, an un- trude from the lateral walls and in children occasionally be-
derstanding of some features and relationships is essential to come so enlarged that exposure of the larynx for intubation
performing intubation. becomes difficult. A large tongue can also cause oropharyn-
geal obstruction. Contraction of the genioglossus muscle nor-
mally moves the tongue forward to open the oropharyngeal
Nose passage during inspiration. Decreased tone of this muscle (e.g.,
in the anesthetized state) can cause obstruction. The orophar-
The roof of the nose is partially formed by the cribriform plate. ynx connects the posterior portion of the oral cavity to the
The anatomic proximity of the roof to intracranial structures hypopharynx.
dictates that special caution be exercised during nasotracheal
intubations. This is particularly true in patients with significant
maxillofacial injuries. Hypopharynx
The mucosa of the nose is provided with a rich blood sup-
ply from branches of the ophthalmic and maxillary arteries, The epiglottis defines the superior border of the hypopharynx,
which allow air to be warmed and humidified. Because the and the beginning of the esophagus forms the inferior bound-
conchae provide an irregular, highly vascularized surface, they ary. The larynx is anterior to the hypopharynx. The pyriform
are particularly susceptible to trauma and subsequent hem- sinuses that extend around both sides of the larynx are part of
orrhage. The orifices from the paranasal sinuses and naso- the hypopharynx.
lacrimal duct open onto the lateral wall. Blockage of these
orifices by prolonged nasotracheal intubation may result in
sinusitis. Larynx
The larynx (Fig. 1.1) is bounded by the hypopharynx superi-
Mouth and Jaw orly and is continuous with the trachea inferiorly. The thyroid,
cricoid, epiglottic, cuneiform, corniculate, and arytenoid carti-
The mouth is formed inferiorly by the tongue, alveolar ridge, lages compose the laryngeal skeleton. The thyroid and cricoid
and mandible. The hard and soft palates compose the supe- cartilages are readily palpated in the anterior neck. The cricoid
rior surface, and the oropharynx forms the posterior surface. cartilage articulates with the thyroid cartilage and is joined to
Assessment of the anatomic features of the mouth and jaw is es- it by the cricothyroid ligament. When the patients head is
sential before orotracheal intubation. A clear understanding of extended, the cricothyroid ligament can be pierced with a
the anatomy is also essential when dealing with a patient who scalpel or large needle to provide an emergency airway (see

1
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2 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

Epiglottis
Trachea
Hyoid
The adult trachea averages 15 cm long. Its external skeleton
Thyrohyoid is composed of a series of C-shaped cartilages. It is bounded
membrane
posteriorly by the esophagus and anteriorly for the first few
Superior horn cartilage rings by the thyroid gland. The trachea is lined with
Thyroid notch ciliated cells that secrete mucus; through the beating action of
Body of thyroid the cilia, foreign substances are propelled toward the larynx.
cartilage The carina is located at the fourth thoracic vertebral level (of
Cricothyroid relevance when judging proper endotracheal tube positioning
membrane on chest radiograph). The right main bronchus takes off at
Cricoid a less acute angle than the left, making right main bronchial
intubation more common if the endotracheal tube is in too far.
Cricotracheal
membrane
EMERGENCY AIRWAY
FIGURE 1.1. Anatomy of the larynx, anterior, and lateral aspects. MANAGEMENT
[From Ellis H: Anatomy for Anaesthetists. Oxford, Blackwell Scien-
tific, 1963, with permission.] In an emergency situation, establishing adequate ventilation
and oxygenation assumes primary importance [3]. Too fre-
quently, inexperienced personnel believe that this requires im-
mediate intubation; however, attempts at intubation may delay
Chapter 12). The cricoid cartilage completely encircles the air- establishment of an adequate airway. Such efforts are time con-
way. It is attached to the first cartilage ring of the trachea by suming, can produce hypoxemia and arrhythmias, and may in-
the cricotracheal ligament. The anterior wall of the larynx is duce bleeding and regurgitation, making subsequent attempts
formed by the epiglottic cartilage, to which the arytenoid carti- to intubate significantly more difficult and contributing to sig-
lages are attached. Fine muscles span the arytenoid and thyroid nificant patient morbidity and even mortality [4,5]. Some sim-
cartilages, as do the vocal cords. The true vocal cords and space ple techniques and principles of emergency airway management
between them are collectively termed the glottis (Fig. 1.2). The can play an important role until the arrival of an individual who
glottis is the narrowest space in the adult upper airway. In is skilled at intubation.
children, the cricoid cartilage defines the narrowest portion
of the airway. Because normal phonation relies on the pre-
cise apposition of the true vocal cords, even a small lesion can Airway Obstruction
cause hoarseness. Lymphatic drainage to the true vocal cords
is sparse. Inflammation or swelling caused by tube irritation Compromised ventilation often results from upper airway ob-
or trauma may take considerable time to resolve. The supe- struction by the tongue, by substances retained in the mouth,
rior and recurrent laryngeal nerve branches of the vagus nerve or by laryngospasm. Relaxation of the tongue and jaw lead-
innervate the structures of the larynx. The superior laryngeal ing to a reduction in the space between the base of the tongue
nerve supplies sensory innervation from the inferior surface and the posterior pharyngeal wall is the most common cause of
of the epiglottis to the superior surface of the vocal cords. upper airway obstruction. Obstruction may be partial or com-
From its takeoff from the vagus nerve, it passes deep to both plete. The latter is characterized by total lack of air exchange.
branches of the carotid artery. A large internal branch pierces The former is recognized by inspiratory stridor and retraction
the thyrohyoid membrane just inferior to the greater cornu of of neck and intercostal muscles. If respiration is inadequate,
the hyoid. This branch can be blocked with local anesthetics the head-tiltchin-lift or jaw-thrust maneuver should be per-
for oral or nasal intubations in awake patients. The recurrent formed. In patients with suspected cervical spine injuries, the
laryngeal branch of the vagus nerve provides sensory inner- jaw-thrust maneuver (without the head tilt) may result in the
vation below the cords. It also supplies all the muscles of the least movement of the cervical spine. To perform the head-tilt
larynx except the cricothyroid, which is innervated by the ex- maneuver, place a palm on the patients forehead and apply
ternal branch of the superior laryngeal nerve. pressure to extend the head about the atlanto-occipital joint.
To perform the chin lift, place several fingers of the other hand
in the submental area and lift the mandible. Care must be taken
to avoid airway obstruction by pressing too firmly on the soft
tissues in the submental area. To perform the jaw thrust, lift up
Epiglottis on the angles of the mandible [3] (Fig. 1.3). Both of these ma-
neuvers open the oropharyngeal passage. Laryngospasm can
be treated by maintaining positive airway pressure using a face
Glottic mask and bag valve device (see the following section). If the
Opening patient resumes spontaneous breathing, establishing this head
position may constitute sufficient treatment. If obstruction per-
sists, a check for foreign bodies, emesis, or secretions should
Vocal be performed [6].
Cords

Use of Face Mask and Bag Valve Device


FIGURE 1.2. Superior view of the larynx (inspiration). [From Stoelt- If an adequate airway has been established and the patient is
ing RH, Miller RD: Basics of Anesthesia. 2nd ed. New York, Churchill not breathing spontaneously, oxygen can be delivered via face
Livingstone, 1989, with permission.] mask and a bag valve device. It is important to establish a
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Chapter 1: Airway Management and Endotracheal Intubation 3

FIGURE 1.3. In an obtunded or comatose patient, the soft tissues of


the oropharynx become relaxed and may obstruct the upper airway.
Obstruction can be alleviated by placing the thumbs on the maxilla
with the index fingers under the ramus of the mandible and rotating
the mandible forward with pressure from the index fingers (arrow).
This maneuver brings the soft tissues forward and therefore frequently
reduces the airway obstruction.

tight fit with the face mask, covering the patients mouth and
FIGURE 1.5. The mechanism of upper airway obstruction and the
nose. To perform this procedure apply the mask initially to the proper position of the oropharyngeal airway. [From Textbook of ad-
bridge of the nose and draw it downward toward the mouth, vanced cardiac life support. Dallas, TX, American Heart Association,
using both hands. The operator stands at the patients head and 1997, with permission.]
presses the mask onto the patients face with the left hand. The
thumb should be on the nasal portion of the mask, the index
finger near the oral portion, and the rest of the fingers spread to establish an adequate airway when proper head positioning
on the left side of the patients mandible so as to pull it slightly alone is insufficient (Figs. 1.4 and 1.5). The oropharyngeal air-
forward. The bag is then alternately compressed and released way is semicircular and made of plastic or hard rubber. The
with the right hand. A good airway is indicated by the rise and two types are the Guedel airway, with a hollow tubular design,
fall of the chest; moreover, lungchest wall compliance can be and the Berman airway, with airway channels along the sides.
estimated from the amount of pressure required to compress Both types are most easily inserted by turning the curved por-
the bag. The minimum effective insufflation pressure should be tion toward the palate as it enters the mouth. It is then advanced
used to decrease the risk of insufflating the stomach with gas beyond the posterior portion of the tongue and rotated down-
and subsequently increase the risk of aspiration. ward into the proper position (Fig. 1.5). Often, depressing the
tongue or moving it laterally with a tongue blade helps to po-
sition the oropharyngeal airway. Care must be exercised not to
Airway Adjuncts push the tongue into the posterior pharynx, causing or exac-
erbating obstruction. Because insertion of the oropharyngeal
If proper positioning of the head and neck or clearance of for- airway can cause gagging or vomiting, or both, it should be
eign bodies and secretions fails to establish an adequate air- used only in unconscious patients.
way, several airway adjuncts may be helpful if an individual The nasopharyngeal airway is a soft tube approximately
who is skilled in intubation is not immediately available. An 15 cm long, which is made of rubber or plastic (Figs. 1.4
oropharyngeal or nasopharyngeal airway occasionally helps and 1.6). It is inserted through the nostril into the posterior

FIGURE 1.4. Nasopharyngeal (A) or


oropharyngeal (B) airways can be used
to relieve soft tissue obstruction if ele-
vating the mandible proves ineffective.
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4 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 1 . 1
INDICATIONS FOR ENDOTRACHEAL INTUBATION

Acute airway obstruction


Trauma
Mandible
Larynx (direct or indirect injury)
Inhalation
Smoke
Noxious chemicals
Foreign bodies
Infection
Acute epiglottitis
Croup
FIGURE 1.6. The proper position of the nasopharyngeal airway. Retropharyngeal abscess
[From Textbook of advanced cardiac life support. Dallas, TX, Ameri- Hematoma
can Heart Association, 1997, with permission.] Tumor
Congenital anomalies
Laryngeal web
pharynx. Before insertion, the airway should be lubricated with Supraglottic fusion
an anesthetic gel, and, preferably, a vasoconstrictor should Laryngeal edema
be administered into the nostril. The nasopharyngeal airway Laryngeal spasm (anaphylactic response)
should not be used in patients with extensive facial trauma or Access for suctioning
cerebrospinal rhinorrhea, as it could be inserted through the Debilitated patients
cribriform plate into the brain. Copious Secretions
Loss of protective reflexes
Head injury
INDICATIONS FOR INTUBATION Drug overdose
The indications for endotracheal intubation can be divided into Cerebrovascular accident
four broad categories: (a) acute airway obstruction, (b) exces- Respiratory failure
sive pulmonary secretions or inability to clear secretions ade- Hypoxemia
quately, (c) loss of protective reflexes, and (d) respiratory failure Acute respiratory distress syndrome
(Table 1.1). Hypoventilation
Atelectasis
Secretions
Preintubation Evaluation Pulmonary edema
Hypercapnia
Even in the most urgent situation, a rapid assessment of the Hypoventilation
patients airway anatomy can expedite the choice of the proper Neuromuscular failure
route for intubation, the appropriate equipment, and the most Drug overdose
useful precautions to be taken. In the less emergent situation,
several minutes of preintubation evaluation can decrease the
likelihood of complications and increase the probability of suc-
cessful intubation with minimal trauma. based on the size of the posterior aspect of the tongue relative to
Anatomic structures of the upper airway, head, and neck the size of the oral pharynx. The patient should be sitting, with
must be examined, with particular attention to abnormalities the head fully extended, protruding the tongue and phonating
that might preclude a particular route of intubation. Evalua- [8]. When the faucial pillars, the uvula, the soft palate, and
tion of cervical spine mobility, temporomandibular joint func- the posterior pharyngeal wall are well visualized, the airway
tion, and dentition is important. Any abnormalities that might is classified as class I, and a relatively easy intubation can be
prohibit alignment of the oral, pharyngeal, and laryngeal axes anticipated. When the faucial pillars and soft palate (class II) or
should be noted. soft palate only (class III) are visible, there is a greater chance of
Cervical spine mobility is assessed by flexion and exten- problems visualizing the glottis during direct laryngoscopy. Dif-
sion of the neck (performed only after ascertaining that no ficulties in orotracheal intubation may also be anticipated if (a)
cervical spine injury exists). The normal range of neck flexion the patient is an adult and cannot open his or her mouth more
extension varies from 165 to 90 degrees, with the range de- than 40 mm (two-finger breadths), (b) the distance from the
creasing approximately 20% by age 75 years. Conditions thyroid notch to the mandible is less than three-finger breadths
associated with decreased range of motion include any cause (less than or equal to 7 cm), (c) the patient has a high arched
of degenerative disk disease (e.g., rheumatoid arthritis, os- palate, or (d) the normal range of flexionextension of the neck
teoarthritis, ankylosing spondylitis), previous trauma, or age is decreased (less than or equal to 80 degrees) [9]. The positive
older than 70 years. Temporomandibular joint dysfunction predictive values of these tests alone or in combination are not
can occur in any form of degenerative arthritis (particularly particularly high; however, a straightforward intubation can
rheumatoid arthritis), in any condition that causes a receding be anticipated if the test results are negative [10]. In the emer-
mandible, and in rare conditions such as acromegaly. gency setting, only about 30% of airways can be assessed in
Examination of the oral cavity is mandatory. Loose, miss- this fashion [11]. A different evaluation method (LEMON) has
ing, or chipped teeth and permanent bridgework are noted, been devised by Murphy and Walls [12]. LEMON stands for
and removable bridgework and dentures should be taken out. look, evaluate, Mallampati class, obstruction, and neck mobil-
Mallampati et al. [7] (Fig. 1.7) developed a clinical indicator ity (Fig. 1.7). In the emergency setting, there are still limitations
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Chapter 1: Airway Management and Endotracheal Intubation 5

L Look externally
Look at the patient externally for characteristics that are known to cause difficult laryngoscopy,
intubation or ventilation.
E Evaluate the 3-3-2 rule
In order to allow alignment of the pharyngeal, laryngeal, and oral axes and therefore simple intubation,
the following relationships should be observed. The distance between the patient's incisor teeth should
be at least 3 finger breadths (3), the distance between the hyoid bone and the chin should be at least
3 finger breadths (3), and the distance between the thyroid notch and the floor of the mouth should be
at least 2 finger breadths (2).
1
2
1 Inter-incisor distance in fingers 3
2 Hyoid mental distance in fingers
3 Thyroid to floor of mouth in
fingers

M Mallampati
The hypopharynx should be visualized adequately. This has been done traditionally by assessing the
Mallampati classification. The patient is sat upright, told to open the mouth fully and protrude the
tongue as far as possible. The examiner then looks into the mouth with a light torch to assess the degree
of hypopharynx visible. In the case of a supine patient, Mallampati score can be estimated by getting
the patient to open the mouth fully and protrude the tongue and a laryngoscopy light can be shone into
the hypopharynx from above.

Class I: soft palate, Class II: soft palate, Class III: soft palate, Class IV: hard palate
uvula, fauces, pillars uvula, fauces visible base of uvula visible only visible
visible
O Obstruction?
Any condition that can cause obstruction of the airway will make laryngoscopy and ventilation difficult.
Such conditions are epiglottis, peritonsillar abscesses, and trauma.
N Neck mobility
This is a vital requirement for successful intubation. It can be assessed easily by getting the patient to
place his or her chin down onto the chest and then to extend the neck so the patient is looking towards the
ceiling. Patients in hard collar neck immobilization obviously have no neck movement and are therefore
harder to intubate.
FIGURE 1.7. The LEMON airway assessment method. [From Reed MJ, Dunn MJ, McKeown DW: Can
an airway assessment score predict difficulty at intubation in the emergency department? Emerg Med J
22(2):99102, 2005, with permission.]

with the use of LEMON since it is difficult to ascertain the Mal- these include neck radiation changes, male sex, a diagnosis
lampati class. Nonetheless, using elements of LEMON that of sleep apnea, Mallampati class III or IV airway, and the
could be incorporated into the emergency evaluation of pa- presence of a beard [14]. Among these factors, neck radiation
tients, Reed et al. [13] found that large incisors, a reduced changes were the most significant predictor of impossible mask
interincisor distance, and a reduced distance between the thy- ventilation.
roid and floor of the mouth were associated with a limited
laryngoscopic view in emergency department patients. When-
ever possible, patients in need of elective and emergent air- Education and Intubation Management
way management should be assessed for indicators of difficult
mask ventilation as this may significantly influence the deci- Emergent intubation in the acute care setting is associated with
sion on the primary approach to airway management. In the a high complication rate. It is therefore important to provide
largest analysis published to date, five independent predictors adequate training to practitioners working in this environment,
of impossible mask ventilation were identified by the authors; and have an adequate number of trained personnel be available
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6 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

to assist the operator. Furthermore, a standardized approach to


emergency airway management can improve patient outcomes. Laryngoscopes
Although training on a mannequin is an important first step in
acquiring competency in performing endotracheal intubation, The two-piece laryngoscope has a handle containing batter-
an investigation including nonanesthesia trainees has shown ies that power the bulb in the blade. The blade snaps securely
that approximately 50 supervised endotracheal intubations in into the top of the handle, making the electrical connection.
the clinical setting are needed to achieve a 90% probability of Failure of the bulb to illuminate suggests improper blade posi-
competent performance [15]. Whenever possible, residents and tioning, bulb failure, a loose bulb, or dead batteries. Modern
licensed independent practitioners should be supervised by an laryngoscope blades with fiberoptic lights obviate the prob-
attending physician trained in emergency airway management lem of bulb failure. Many blade shapes and sizes are avail-
during the procedure. This approach has led to a significant able. The two most commonly used blades are the curved
reduction in immediate complications from 21.7% to 6.1% in (MacIntosh) and straight (Miller) blades (Fig. 1.8). Although
one pre- and postintervention analysis [16]. pediatric blades are available for use with the adult-sized han-
In addition, the use of a management bundle consisting of dle, most anesthesiologists prefer a smaller handle for bet-
interventions that, in isolation have been shown to decrease ter control in the pediatric population. The choice of blade
complications during emergency airway management can fur- shape is a matter of personal preference and experience; how-
ther improve patient outcomes. Elements that should be in- ever, one study has suggested that less force and head exten-
cluded in this approach are preoxygenation with noninvasive sion are required when performing direct laryngoscopy with
positive pressure ventilation (NIPPV) if feasible, presence of a straight blade [18]. Recently, video assisted laryngoscopes
two operators, rapid sequence intubation (RSI) with cricoid have become widely available in many perioperative and acute
pressure, capnography, lung protective ventilation strategies care specialties. These have been shown to improve the suc-
(LPVS), fluid loading prior to intubation unless contraindi- cess rate for difficult endotracheal intubation performed by
cated, and preparation and early administration of sedation experienced physicians [19], as well as the rate of successful
and vasopressor use if needed [17]. intubation by untrained individuals when performing normal
intubations [20]. Several online tutorials are available demon-
strating the use of video laryngoscopes. Two of them can be
found here: Turk M, Gravenstein D (2007): Storz DCI Video
EQUIPMENT FOR INTUBATION Laryngoscope. Retrieved March 15, 2010, from University
of Florida Department of Anesthesiology, Center for Simula-
Assembly of all appropriate equipment before attempted intu- tion, Advanced Learning and Technology Web site: http://vam.
bation can prevent potentially serious delays in the event of anest.ufl.edu/airwaydevice/storz/index.html and http://www.
an unforeseen complication. Most equipment and supplies are youtube.com/watch?v=WdooBCJ79Xc&NR=1. Hagberg has
readily available in the ICU but must be gathered so they are compiled an extensive list of commercially available video-
immediately at hand. A supply of 100% oxygen and a well- laryngoscopes [21].
fitting mask with attached bag valve device are mandatory, as is
suctioning equipment, including a large-bore tonsil suction at-
tachment (Yankauer) and suction catheters. Adequate lighting
facilitates airway visualization. The bed should be at the proper Endotracheal Tubes
height, with the headboard removed and the wheels locked.
Other necessary supplies include gloves, Magill forceps, oral The internal diameter of the endotracheal tube is measured us-
and nasal airways, laryngoscope handle and blades (straight ing both millimeters and French units. This number is stamped
and curved), endotracheal tubes of various sizes, stylet, tongue on the tube. Tubes are available in 0.5-mm increments, starting
depressors, a syringe for cuff inflation, and tape for securing at 2.5 mm. Lengthwise dimensions are also marked on the tube
the endotracheal tube in position. Table 1.2 is a checklist of in centimeters, beginning at the distal tracheal end.
supplies needed. Selection of the proper tube diameter is of utmost impor-
tance and is a frequently underemphasized consideration. The
TA B L E 1 . 2 resistance to airflow varies with the fourth power of the radius
of the endotracheal tube. Thus, selection of an inappropriately
EQUIPMENT NEEDED FOR INTUBATION small tube can significantly increase the work of breathing.
Moreover, certain diagnostic procedures (e.g., bronchoscopy)
Supply of 100% oxygen done through endotracheal tubes require appropriately large
Face mask tubes (see Chapter 9). In general, the larger the patient, the
Bag valve device larger the endotracheal tube that should be used. Approximate
Suction equipment guidelines for tube sizes and lengths by age are summarized
Suction catheters in Table 1.3. Most adults should be intubated with an endo-
Large-bore tonsil suction apparatus (Yankauer) tracheal tube that has an inner diameter of at least 8.0 mm,
Stylet although occasionally nasal intubation in a small adult requires
Magill forceps a 7.0-mm tube.
Oral airways
Nasal airways
Laryngoscope handle and blades (curved, straight; various
sizes) Endotracheal Tube Cuff
Endotracheal tubes (various sizes)
Tongue depressors Endotracheal tubes have low-pressure, high-volume cuffs to re-
Syringe for cuff inflation duce the incidence of ischemia-related complications. Tracheal
Headrest ischemia can occur any time cuff pressure exceeds capillary
Supplies for vasoconstriction and local anesthesia pressure (approximately 32 mm Hg), thereby causing inflam-
Tape mation, ulceration, infection, and dissolution of cartilaginous
Tincture of benzoin rings. Failure to recognize this progressive degeneration some-
times results in erosion through the tracheal wall (into the
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Chapter 1: Airway Management and Endotracheal Intubation 7

A B

FIGURE 1.8. The two basic types of laryngoscope blades, MacIntosh (A) and Miller (B). The MacIntosh
blade is curved. The blade tip is placed in the vallecula and the handle of the laryngoscope pulled forward
at a 45-degree angle. This allows visualization of the epiglottis. The Miller blade is straight. The tip is
placed posterior to the epiglottis, pinning the epiglottis between the base of the tongue and the straight
laryngoscope blade. The motion on the laryngoscope handle is the same as that used with the MacIntosh
blade.

innominate artery if the erosion was anterior or the esoph-


agus if the erosion was posterior) or long-term sequelae of ANESTHESIA BEFORE
tracheomalacia or tracheal stenosis. With cuff pressures of 15 INTUBATION
to 30 mm Hg, the low-pressure, high-volume cuffs conform
well to the tracheal wall and provide an adequate seal during Because patients who require intubation often have a depressed
positive-pressure ventilation. Although low cuff pressures can level of consciousness, anesthesia is usually not required. If in-
cause some damage (primarily ciliary denudation), major com- tubation must be performed on the alert, responsive patient,
plications are rare. Nevertheless, it is important to realize that sedation or general anesthesia exposes the individual to po-
a low-pressure, high-volume cuff can be converted to a high- tential pulmonary aspiration of gastric contents because pro-
pressure cuff if sufficient quantities of air are injected into the tective reflexes are lost. This risk is a particularly important
cuff. consideration if the patient has recently eaten and must be

TA B L E 1 . 3
DIMENSIONS OF ENDOTRACHEAL TUBES BASED ON PATIENT AGE

Distance between lips and


location in midtrachea of
Age Internal diameter (mm) French unit distal end (cm)a

Premature 2.5 1012 10


Full term 3.0 1214 11
16 mo 3.5 16 11
612 mo 4.0 18 12
2y 4.5 20 13
4y 5.0 22 14
6y 5.5 24 1516
8y 6.5 26 1617
10 y 7.0 28 1718
12 y 7.5 30 1820
14 y 8.09.0 3236 2024
a
Add 2 to 3 cm for nasal tubes.
From Stoelting RK: Endotracheal intubation, in Miller RD (ed): Anesthesia. 2nd ed. New
York, Churchill Livingstone, 1986, p. 531, with permission.
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8 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 1 . 4
DRUGS USED TO FACILITATE INTUBATION

Drug IV dose (mg/kg) Onset of action (sec) Side effects

Induction drugs
Thiopental 2.54.5 2050 Hypotension
Propofol 1.02.5 <60 Pain on injection
Hypotension
Midazolam 0.020.20 3060 Hypotension
Ketamine 0.52.0 3060 Increases in intracranial pressure
Increase in secretions
Emergence reactions
Etomidate 0.20.3 2050 Adrenal insufficiency
Pain on injection
Muscle relaxants
Succinylcholine 12 4560 Hyperkalemia
Increased intragastric pressure
Increased intracranial pressure
Rocuronium 0.61.0 6090

weighed against the risk of various hemodynamic derange- bone. The rate of absorption of lidocaine differs by method,
ments that might occur secondary to tracheal intubation and being greater with the aerosol and transtracheal techniques.
initiation of positive-pressure ventilation. Laryngoscopy in an The patient should be observed for signs of lidocaine toxicity
inadequately anesthetized patient can result in tachycardia and (circumoral paresthesia, agitation, and seizures).
an increase in blood pressure. This may be well tolerated in If adequate topical anesthesia cannot be achieved or if the
younger patients but may be detrimental in a patient with patient is not cooperative, general anesthesia may be required
coronary artery disease or raised intracranial pressure. Some- for intubation. Table 1.4 lists common drugs and doses that
times laryngoscopy and intubation may result in a vasovagal are used to facilitate intubation. Ketamine and etomidate are
response, leading to bradycardia and hypotension. Initiation of two drugs that are used commonly because cardiovascular sta-
positive-pressure ventilation in a hypovolemic patient can lead bility is maintained. Caution should be exercised when using
to hypotension from diminished venous return. etomidate in patients with signs and symptoms consistent with
Some of these responses can be attenuated by providing severe sepsis or septic shock. In an analysis of risk factors of rel-
local anesthesia to the nares, mouth, and/or posterior phar- ative adrenocortical deficiency in intensive care patients need-
ynx before intubation. Topical lidocaine (1% to 4%) with ing mechanical ventilation, single bolus etomidate administra-
phenylephrine (0.25%) or cocaine (4%, 200 mg total dose) tion was independently associated with relative adrenocortical
can be used to anesthetize the nasal passages and provide local deficiency [24]. Similarly, when studied for rapid sequence in-
vasoconstriction. This allows the passage of a larger endotra- tubation in acutely ill patients both ketamine and etomidate
cheal tube with less likelihood of bleeding. Aqueous lidocaine provided adequate intubating conditions but the percentage of
phenylephrine or cocaine can be administered via atomizer, patients with adrenal insufficiency was significantly higher in
nose dropper, or long cotton-tipped swabs inserted into the the etomidate group [25]. Lastly, post hoc analysis of the cor-
nares. Alternatively, viscous 2% lidocaine can be applied via ticosteroid therapy of septic shock study revealed an increased
a 3.5-mm endotracheal tube or small nasopharyngeal airway rate of death at 28 days among patients who received etomidate
inserted into the nose. Anesthesia of the tongue and poste- before randomization in both groups (hydrocortisone group
rior pharynx can be accomplished with lidocaine spray (4% and in the placebo group), as compared with patients who did
to 10%) administered via an atomizer or an eutectic mixture not receive etomidate [26]. Taken together these findings war-
of local anesthetics cream applied on a tongue blade and oral rant a careful analysis of risks and benefits before etomidate is
airway [22]. Alternatively, the glossopharyngeal nerve can be used to facilitate endotracheal intubation in acutely ill patients
blocked bilaterally with an injection of a local anesthetic, but with, or at risk for, severe sepsis.
this should be performed by experienced personnel. Use of opioids such as morphine, fentanyl, sufentanil, alfen-
Anesthetizing the larynx below the vocal cords before intu- tanil, or remifentanil allow the dose of the induction drugs to
bation is controversial. The cough reflex can be compromised, be reduced and may attenuate the hemodynamic response
increasing the risk of aspiration. However, tracheal anesthesia to laryngoscopy and intubation. Muscle relaxants can be used
may decrease the incidence of arrhythmias or untoward circu- to facilitate intubation, but unless the practitioner has extensive
latory responses to intubation and improve patient tolerance experience with these drugs and airway management, alterna-
of the endotracheal tube. Clinical judgment in this situation tive means of airway control and oxygenation should be used
is necessary. Several methods can be used to anesthetize these until an anesthesiologist arrives to administer the anesthetic
structures. Transtracheal lidocaine (4%, 160 mg) is adminis- and perform the intubation. Although the use of muscle relax-
tered by cricothyroid membrane puncture with a small needle ants is associated with improved laryngoscopy grade during
to anesthetize the trachea and larynx below the vocal cords. Al- intubation, their use may not be associated with a decrease in
ternatively, after exposure of the vocal cords with the laryngo- overall airway related complications, hypotension or hypox-
scope, the cords can be sprayed with lidocaine via an atomizer. emia.
Aerosolized lidocaine (4%, 6 mL) provides excellent anesthesia Recent reviews have extolled the virtue of rapid sequence
to the mouth, pharynx, larynx, and trachea [23]. The superior intubation (RSI) [27,28]: The process by which a drug such
laryngeal nerve can be blocked with 2 mL of 1.0% to 1.5% as etomidate, thiopental, ketamine, or propofol (Table 1.4) is
lidocaine injected just inferior to the greater cornu of the hyoid administered to the patient to induce anesthesia and is followed
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Chapter 1: Airway Management and Endotracheal Intubation 9

immediately by a muscle relaxant to facilitate intubation. Al-


though numerous studies exist in the emergency medicine lit- Specific Techniques and Routes of
erature attesting to the safety and efficacy of this approach, Endotracheal Intubation
the practitioner who embarks on this route to intubation in
the ICU must be knowledgeable about the pharmacology and Orotracheal Intubation
side effects of the agents used and the use of rescue meth-
ods should attempt(s) at intubation fail. Again, experience and Orotracheal intubation is the technique most easily learned and
an approached based on a validated algorithm will increase most often used for emergency intubations in the ICU. Tra-
patient safety. In a recent analysis of 6,088 trauma patients ditional teaching dictates that successful orotracheal intuba-
undergoing emergency airway management in a single center tion requires alignment of the oral, pharyngeal, and laryngeal
over 10 years, intubation by anesthesiologists experienced in axes by putting the patient in the sniffing position in which
the management of trauma patients utilizing a modification the neck is flexed and the head is slightly extended about the
of the American Society of Anesthesiologists difficult airway atlanto-occipital joint. However, a magnetic resonance imag-
algorithm was very effective, resulting in a rate of surgical ing (MRI) study has called this concept into question, as the
airway management in only 0.3% of patients included in the alignment of these three axes could not be achieved in any of
analysis [29]. the three positions tested: neutral, simple extension, and the
sniffing position [35]. In addition, a randomized study in
elective surgery patients examining the utility of the sniffing
position as a means to facilitate orotracheal intubation failed
TECHNIQUES OF INTUBATION to demonstrate that such positioning was superior to simple
head extension [36].
In a true emergency, some of the preintubation evaluation is In a patient with a full stomach, compressing the cricoid
necessarily neglected in favor of rapid control of the airway. cartilage posteriorly against the vertebral body can reduce
Attempts at tracheal intubation should not cause or exacer- the diameter of the postcricoid hypopharynx. This technique,
bate hypoxia. Whenever possible, an oxygen saturation mon- known as Sellicks maneuver, may prevent passive regurgita-
itor should be used. Preoxygenation (denitrogenation), which tion of stomach contents into the trachea during intubation
replaces the nitrogen in the patients functional residual capac- [37]. However, an MRI study of awake volunteers demon-
ity with oxygen, can maximize the time available for intuba- strated that the esophagus was lateral to the larynx in more
tion. During laryngoscopy, apneic oxygenation can occur from than 50% of the subjects. Moreover, cricoid pressure increased
this reservoir. Preoxygenation is achieved by providing 100% the incidence of an unopposed esophagus by 50% and caused
oxygen at a high flow rate via a tight-fitting face mask for 3.5 to airway compression of greater than 1 mm in 81% of the vol-
4.0 minutes. Extending the time of preoxygenation from 4 to unteers [38]. These findings are in contrast to a more recent
8 minutes does not seem to increase the PaO2 to a clinically rel- MRI study demonstrating that the location and movement of
evant extent and may actually reduce the PaO2 in the interval the esophagus is irrelevant to the efficacy of Sellicks maneu-
from 6 to 8 minutes in some patients [30]. In patients who are ver to prevent gastric regurgitation into the pharynx. Of note,
being intubated for airway control, preoxygenation is usually compression of the alimentary tract was demonstrated with
efficacious; whereas, the value of preoxygenation in patients midline and lateral displacement of the cricoid cartilage rela-
with acute lung injury is less certain [31]. Whenever possi- tive to the underlying vertebral body [39]. In addition, cadaver
ble, NIPPV should be utilized as the mode of preoxygenation studies have demonstrated the efficacy of cricoid pressure [40]
prior to intubation of hypoxemic patients. This approach has and clinical studies have shown that gastric insufflation with
been shown to be more effective than the standard approach gas during mask ventilation is reduced when cricoid pressure is
in maintaining SpO2 values before, during and even after the applied [41]. In aggregate, these data suggest that it is prudent
intubation procedure resulting [32]. In obese patients, use of to continue to use cricoid pressure in patients suspected of hav-
the 25-degree head-up position improves the effectiveness of ing full stomachs. In addition, placing the patient in the partial
preoxygenation [33]. recumbent or reverse Trendelenburg position may reduce the
Just before intubation, the physician should assess the like- risk of regurgitation and aspiration.
lihood of success for each route of intubation, the urgency of The laryngoscope handle is grasped in the left hand while
the clinical situation, the likelihood that intubation will be the patients mouth is opened with the gloved right hand. Of-
prolonged, and the prospect of whether diagnostic or ther- ten, when the head is extended in the unconscious patient, the
apeutic procedures such as bronchoscopy will eventually be mouth opens; if not, the thumb and index finger of the right
required. Factors that can affect patient comfort should also hand are placed on the lower and upper incisors, respectively,
be weighed. In the unconscious patient in whom a secure air- and moved past each other in a scissor-like motion. The laryn-
way must be established immediately, orotracheal intubation goscope blade is inserted on the right side of the mouth and
with direct visualization of the vocal cords is generally the pre- advanced to the base of the tongue, pushing it toward the left.
ferred technique. In the conscious patient, direct laryngoscopy If the straight blade is used, it should be extended below the
or awake fiberoptic intubation may be performed after ade- epiglottis. If the curved blade is used, it is inserted in the val-
quate topicalization of the airway. Alternatively, blind naso- lecula.
tracheal intubation is an option but requires significant skill With the blade in place, the operator should lift forward in a
by the clinician. Nasotracheal intubation should be avoided plane 45 degrees from the horizontal to expose the vocal cords
in patients with coagulopathies or those who are anticoagu- (Figs. 1.2 and 1.8). This motion decreases the risk of the blade
lated for medical indications. In trauma victims with exten- striking the upper incisors and either chipping or dislodging
sive maxillary and mandibular fractures and inadequate ven- teeth. Both lips should be swept away from between the teeth
tilation or oxygenation, cricothyrotomy may be mandatory and blade to avoid soft tissue damage. The endotracheal tube is
(see Chapter 12). In patients with cervical spine injury or de- then held in the right hand and inserted at the right corner of the
creased neck mobility, intubation using the flexible broncho- patients mouth in a plane that intersects with the laryngoscope
scope or specialized laryngoscope (Bullard) may be necessary. blade at the level of the glottis. This prevents the endotracheal
Many of these techniques require considerable skill and should tube from obscuring the view of the vocal cords. The endotra-
be performed only by those who are experienced in airway cheal tube is advanced through the vocal cords until the cuff
management [34]. just disappears from sight. The cuff is inflated with enough air
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10 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

Grade I Grade II Grade III Grade IV

FIGURE 1.9. The four grades of laryngeal view during direct laryngoscopy. Grade I: the entire glottis is
seen. Grade II: only the posterior aspect of the glottis is seen. Grade III: only the epiglottis is seen. Grade
IV: the epiglottis is not visualized. [From Cormack RS, Lehane J: Difficult tracheal intubation in obstetrics.
Anaesthesia 39:11051111, 1984, with permission.]

to prevent a leak during positive-pressure ventilation with a of the endotracheal tube and changes color on exposure to
bag valve device. carbon dioxide. An additional method to detect esophageal in-
A classification grading the view of the laryngeal aper- tubation uses a bulb that attaches to the proximal end of the
ture during direct laryngoscopy has been described [42] and endotracheal tube [47]. The bulb is squeezed. If the tube is in
is depicted in Figure 1.9. Occasionally, the vocal cords can- the trachea, the bulb reexpands, and if the tube is in the esoph-
not be seen entirely; only the corniculate and cuneiform tuber- agus, the bulb remains collapsed. It must be remembered that
cles, interarytenoid incisure, and posterior portion of the vocal none of these techniques is foolproof. Bronchoscopy is the only
cords or only the epiglottis is visualized (grades II to IV view; method to be absolutely sure the tube is in the trachea. After
Fig. 1.9). In this situation, it is helpful to insert the soft metal estimating proper tube placement clinically, it should be con-
stylet into the endotracheal tube and bend it into a hockey- firmed by chest radiograph or bronchoscopy because the tube
stick configuration. The stylet should be bent or coiled at the may be malpositioned. The tip of the endotracheal tube should
proximal end to prevent the distal end from extending beyond be several centimeters above the carina (T-4 level). It must be
the endotracheal tube and causing tissue damage. The stylet remembered that flexion or extension of the head can advance
should be lubricated to ensure easy removal. The BURP ma- or withdraw the tube 2 to 5 cm, respectively.
neuver (backwardupwardr ightward pressure on the larynx)
improves the view of the laryngeal aperture [43]. Alternatively,
a control-tip endotracheal tube can be used. This tube has a Nasotracheal Intubation
nylon cord running the length of the tube attached to a ring Many of the considerations concerning patient preparation and
at the proximal end, which allows the operator to direct the positioning outlined for orotracheal intubation apply to nasal
tip of the tube anteriorly. Another aid is a stylet with a light intubation as well. Blind nasal intubation is more difficult to
(light wand). With the room lights dimmed, the endotracheal perform than oral intubation, because the tube cannot be ob-
tube containing the lighted stylet is inserted into the orophar- served directly as it passes between the vocal cords. However,
ynx and advanced in the midline. When it is just superior to nasal intubation is usually more comfortable for the patient and
the larynx, a glow is seen over the anterior neck. The stylet is is generally preferable in the awake, conscious patient. Nasal
advanced into the trachea, and the tube is threaded over it. The intubation should not be attempted in patients with abnor-
light intensity is diminished if the wand enters the esophagus mal bleeding parameters, nasal polyps, extensive facial trauma,
[44]. The gum elastic bougie (flexible stylet) is another alterna- cerebrospinal rhinorrhea, sinusitis, or any anatomic abnormal-
tive device that can be passed into the larynx; once in place, the ity that would inhibit atraumatic passage of the tube.
endotracheal tube is advance over it and the stylet is removed. As previously discussed in Airway Adjuncts section, after
Endotracheal tubes and stylets are now available that have a the operator has alternately occluded each nostril to ascertain
fiberoptic bundle intrinsic to the tube or the stylet that can be that both are patent, a topical vasoconstrictor and anesthetic
attached to a video monitor. If the attempt to intubate is still un- are applied to the nostril that will be intubated. The nostril
successful, the algorithm that is described in the Management may be dilated with lubricated nasal airways of increasing size
of the Difficult Airway section should be followed. to facilitate atraumatic passage of the endotracheal tube. The
Proper depth of tube placement is clinically ascertained by patient should be monitored with a pulse oximeter, and sup-
observing symmetric expansion of both sides of the chest and plemental oxygen should be given as necessary. The patient
auscultating equal breath sounds in both lungs. The stomach may be either supine or sitting with the head extended in the
should also be auscultated to ensure that the esophagus has sniffing position. The tube is guided slowly but firmly through
not been entered. If the tube has been advanced too far, it the nostril to the posterior pharynx. Here the tube operator
will lodge in one of the main bronchi (particularly the right must continually monitor for the presence of air movement
bronchus), and only one lung will be ventilated. If this error through the tube by listening for breath sounds with the ear
goes unnoticed, the nonventilated lung may collapse. A use- near the open end of the tube. The tube must never be forced
ful rule of thumb for tube placement in adults of average size or pushed forward if breath sounds are lost, because damage
is that the incisors should be at the 23-cm mark in men and to the retropharyngeal mucosa can result. If resistance is met,
the 21-cm mark in women [45]. Alternatively, proper depth the tube should be withdrawn 1 to 2 cm and the patients head
(5 cm above the carina) can be estimated using the following repositioned (extended further or turned to either side). If the
formula: (height in cm/5) minus 13 [46]. Palpation of the an- turn still cannot be negotiated, the other nostril or a smaller
terior trachea in the neck may detect cuff inflation as air is tube should be tried. Attempts at nasal intubation should be
injected into the pilot tube and can serve as a means to ascer- abandoned and oral intubation performed if these methods fail.
tain correct tube position. Measurement of end-tidal carbon Once positioned in the oropharynx, the tube should be ad-
dioxide by standard capnography if available or by means of vanced to the glottis while listening for breath sounds through
a calorimetric chemical detector of end-tidal carbon dioxide the tube. If breath sounds cease, the tube is withdrawn several
(e.g., Easy Cap II, Nellcor, Inc., Pleasanton, CA) can be used to centimeters until breath sounds resume, and the plane of en-
verify correct endotracheal tube placement or detect esophageal try is adjusted slightly. Passage through the vocal cords should
intubation. The latter device is attached to the proximal end be timed to coincide with inspiration. Entry of the tube into
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Chapter 1: Airway Management and Endotracheal Intubation 11

the larynx is signaled by an inability to speak. The cuff should


be inflated and proper positioning of the tube ascertained as
previously outlined.
Occasionally, blind nasal intubation cannot be accom-
plished. In this case, after adequate topical anesthesia, laryn-
goscopy can be used to visualize the vocal cords directly and
Magill forceps used to grasp the distal end of the tube and guide
it through the vocal cords (Fig. 1.10). Assistance in pushing the
tube forward is essential during this maneuver, so that the op-
erator merely guides the tube. The balloon on the tube should
not be grasped with the Magill forceps.
Occasionally, one may not be able to successfully place the
endotracheal tube in the trachea. The technique of managing a
difficult airway is detailed later.

Management of the Difficult Airway


A difficult airway may be recognized (anticipated) or unrecog-
nized at the time of the initial preintubation airway evaluation.
Difficulty managing the airway may be the result of abnormali-
ties such as congenital hypoplasia, hyperplasia of the mandible
or maxilla, or prominent incisors; injuries to the face or neck;
FIGURE 1.10. Magill forceps may be required to guide the endo- acromegaly; tumors; and previous head and neck surgery. Dif-
tracheal tube into the larynx during nasotracheal intubation. [From ficulties ventilating the patient with a mask can be anticipated
Barash PG, Cullen BF, Stoelting RK: Clinical Anesthesia. 2nd ed. if two of the following factors are present: age older than 55
Philadelphia, PA, JB Lippincott Co, 1992, with permission.] years, body mass index greater than 26 kg per m2 , beard, lack
of teeth, and a history of snoring [48]. When a difficult air-
way is encountered, the algorithm as detailed in Figure 1.11

Algorithm for airway management in the ICU

Airway management
necessary

Call senior physician


for assistance

Invasive airway Noninvasive airway


management management

Fails
NIPPV

Potential for DMV Yes, adequate Primary awake technique


and/or DI physiologic reserve (FOI, nasotracheal)

Yes, pt in Supralaryngeal ventilation


No respiratory arrest as conduit for intubation

Direct Laryngoscopy
Ablation vs. preservation of No Yes
SB, with or without NMBA
FIGURE 1.11. Modification of the difficult air-
Intubating-, video- way algorithm. ASA DAA, American Society
Fails, mask of Anesthesiologists difficult airway algorithm;
Fails, mask assisted-, or classic LMA
ventilation DMV, difficult mask ventilation; FOI, fiberoptic
ventilation as bridge for definitive
adequate intubation; LMA, laryngeal mask airway; NIPPV,
inadequate airway mgt
noninvasive positive pressure ventilation; NMBA,
neuromuscular blocking agents; SB, spontaneous
breathing. [From Walz JM, Zayaruzny M, Heard
ASA DAA emergency pathway(s) SO, et al. Chest 131(2):608620, 2007, with per-
mission.]
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12 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

should be followed [49]. When a difficult airway is recognized If the operator is able to maintain mask ventilation in a
before the patient is anesthetized, an awake tracheal intuba- patient with an unrecognized difficult airway, a call for expe-
tion is usually the best option. Multiple techniques can be used rienced help should be initiated (Fig. 1.11). If mask ventilation
and include (after adequate topical or local anesthesia) direct cannot be maintained, a cannot ventilatecannot intubate sit-
laryngoscopy, LMA (or variants), blind or bronchoscopic oral uation exists and immediate lifesaving rescue maneuvers are
or nasal intubation, retrograde technique, rigid bronchoscopy, required. Options include an emergency cricothyrotomy or in-
lighted stylet, or a surgical airway. sertion of a supraglottic ventilatory device, such as an LMA or
a Combitube. (Puritan Bennett, Pleasanton, CA.)

Flexible Bronchoscopic Intubation Other Airway Adjuncts


Flexible bronchoscopy is an efficacious method of intubat- The LMA is composed of a plastic tube attached to a shal-
ing the trachea in difficult cases. It may be particularly useful low mask with an inflatable rim (Fig. 1.12). When properly
when the upper airway anatomy has been distorted by tumors, inserted, it fits over the laryngeal inlet and allows positive-
trauma, endocrinopathies, or congenital anomalies. This tech- pressure ventilation of the lungs. Although aspiration can oc-
nique is sometimes valuable in accident victims in whom a ques- cur around the mask, the LMA can be lifesaving in a can-
tion of cervical spine injury exists and the patients neck can- not ventilatecannot intubate situation. An intubating LMA
not be manipulated. An analogous situation exists in patients (LMA-Fastrach, LMA North America, Inc., San Diego, CA)
with severe degenerative disk disease of the neck or rheuma- has a shorter plastic tube and can be used to provide ventila-
toid arthritis with markedly impaired neck mobility. After ad- tion as well as to intubate the trachea with or without the aid
equate topical anesthesia is obtained as described in the sec- of a flexible bronchoscope (Fig. 1.13). The Combitube (Puritan
tion Anesthesia before Intubation, the bronchoscope can be Bennett, Pleasanton, CA) combines the features of an endotra-
used to intubate the trachea via either the nasal or oral route. cheal tube and an esophageal obturator airway and reduces
An appropriately sized warmed and lubricated endotracheal the risk of aspiration. Personnel who are unskilled in airway
tube that has been preloaded onto the bronchoscope is ad- management can easily learn how to use the LMA and the
vanced through the vocal cords into the trachea and positioned Combitube together [50].
above the carina under direct vision. The flexible bronchoscope
has also been used as a stent over which endotracheal tubes are
exchanged and as a means to assess tracheal damage period-
Cricothyrotomy
ically during prolonged intubations. (A detailed discussion of In a truly emergent situation, when intubation is unsuccess-
bronchoscopy is found in Chapter 9.) Intubation by this tech- ful, a cricothyrotomy may be required. The technique is de-
nique requires skill and experience and is best performed by a scribed in detail in Chapter 12. The quickest method, needle
fully trained operator. cricothyrotomy, is accomplished by introducing a large-bore

A B

FIGURE 1.12. Technique for insertion


of the laryngeal mask airway. [From
Civetta JM, Taylor RW, Kirby RR: Crit-
ical Care. 3rd ed. Philadelphia, PA,
LippincottRaven Publishers, 1997,
C D with permission.]
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Chapter 1: Airway Management and Endotracheal Intubation 13

extubation, (b) to prevent advancement into one of the main


D bronchi, and (c) to minimize damage to the upper airway, lar-
ynx, and trachea caused by patient motion. The endotracheal
tube is usually secured in place with adhesive tape wrapped
C around the tube and applied to the patients cheeks. Tincture
of benzoin sprayed on the skin provides greater fixation. Alter-
natively, tape, intravenous (IV) tubing, or umbilical tape can
be tied to the endotracheal tube and brought around the pa-
tients neck to secure the tube. Care must be taken to prevent
B occlusion of neck veins. Other products (e.g., Velcro straps) to
secure the tube are available. A bite block can be positioned in
patients who are orally intubated to prevent them from biting
down on the tube and occluding it. Once the tube has been
secured and its proper position verified, it should be plainly
marked on the portion protruding from the patients mouth or
A
nose so that advancement can be noted.

Cuff Management
Although low-pressure cuffs have markedly reduced the inci-
dence of complications related to tracheal ischemia, monitoring
FIGURE 1.13. The laryngeal mask airway (LMA)-Fastrach (A) has a cuff pressures remains important. The cuff should be inflated
shorter tube than a conventional LMA. A special endotracheal tube just beyond the point where an audible air leak occurs. Mainte-
(B) [without the adapter (C)] is advanced through the LMA-Fastrach nance of intracuff pressures between 17 and 23 mm Hg should
into the trachea. The extender (D) is attached to the endotracheal tube, allow an adequate seal to permit mechanical ventilation under
and the LMA-Fastrach is removed. After the extender is removed, the most circumstances while not compromising blood flow to the
adapter is placed back on the tube. tracheal mucosa. The intracuff pressure should be checked pe-
riodically by attaching a pressure gauge and syringe to the cuff
port via a three-way stopcock. The need to add air continually
(i.e., 14-gauge) catheter into the airway through the cricothy- to the cuff to maintain its seal with the tracheal wall indicates
roid membrane while aspirating with a syringe attached to the that (a) the cuff or pilot tube has a hole in it, (b) the pilot
needle of the catheter. When air is aspirated, the needle is in tube valve is broken or cracked, or (c) the tube is positioned
the airway and the catheter is passed over the needle into the incorrectly, and the cuff is between the vocal cords. The tube
trachea. The needle is attached to a high-frequency jet venti- position should be reevaluated to exclude the latter possibility.
lation apparatus. Alternatively, a 3-mL syringe barrel can be If the valve is broken, attaching a three-way stopcock to it will
connected to the catheter. Following this, a 7-mm inside diam- solve the problem. If the valve housing is cracked, cutting the
eter endotracheal tube adapter is fitted into the syringe and is pilot tube and inserting a blunt needle with a stopcock into the
connected to a high-pressure gas source or a high-frequency jet lumen of the pilot tube can maintain a competent system. A
ventilator. An algorithm with suggestions for the management hole in the cuff necessitates a change of tube.
of the difficult airway is provided in Figure 1.11.
Tube Suctioning
Management of the Airway in Patients with Suspected A complete discussion of tube suctioning can be found in Chap-
Cervical Spine Injury ter 62. Routine suctioning should not be performed in patients
Any patient with multiple trauma who requires intubation in whom secretions are not a problem. Suctioning can produce
should be treated as if cervical spine injury were present. In a variety of complications, including hypoxemia, elevations
the absence of severe maxillofacial trauma or cerebrospinal in intracranial pressure, and serious ventricular arrhythmias.
rhinorrhea, nasal intubation can be considered. However, in Preoxygenation should reduce the likelihood of arrhythmias.
the profoundly hypoxemic or apneic patient, the orotracheal Closed ventilation suction systems (Stericath) may reduce the
approach should be used. If oral intubation is required, an risk of hypoxemia but have not been shown to reduce the rate
assistant should maintain the neck in the neutral position by of ventilator-associated pneumonia (VAP) compared to open
ensuring axial stabilization of the head and neck as the patient suction systems [52].
is intubated [51]. A cervical collar also assists in immobiliz-
ing the cervical spine. In a patient with maxillofacial trauma Humidification
and suspected cervical spine injury, retrograde intubation can Intubation of the trachea bypasses the normal upper airway
be performed by puncturing the cricothyroid membrane with structures responsible for heating and humidifying inspired air.
an 18-gauge catheter and threading a 125-cm Teflon-coated It is thus essential that inspired air be heated and humidified
(0.025-cm diameter) guidewire through the catheter. The wire (see Chapter 62).
is advanced into the oral cavity, and the endotracheal tube is
then advanced over the wire into the trachea. Alternatively, the Tube Replacement
wire can be threaded through the suction port of a 3.9-mm
bronchoscope. At times, endotracheal tubes may need to be replaced because of
an air leak, obstruction, or other problems. Before attempting
to change an endotracheal tube, one should assess how difficult
Airway Management in the Intubated Patient it will be. After obtaining appropriate topical anesthesia or IV
sedation and achieving muscle relaxation, direct laryngoscopy
can be performed to ascertain whether there will be difficulties
Securing the Tube in visualizing the vocal cords. If the cords can be seen, the defec-
Properly securing the endotracheal tube in the desired posi- tive tube is removed under direct visualization and reintubation
tion is important for three reasons: (a) to prevent accidental performed using the new tube. If the cords cannot be seen on
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14 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

direct laryngoscopy, the tube can be changed over an airway the pharynx, larynx, or trachea; dislocation of an arytenoid
exchange catheter (e.g., Cook Critical Care, Bloomington, IN) cartilage; retropharyngeal perforation; epistaxis; hypoxemia;
which allows insufflation of oxygen via either standard oxygen myocardial ischemia; laryngospasm with noncardiogenic pul-
tubing or a bag valve device [53]. monary edema; and death [5,54]. Many of these complications
can be avoided by paying careful attention to technique and
ensuring that personnel with the greatest skill and experience
COMPLICATIONS OF perform the intubation. Complications during endotracheal in-
tubation vary according to the location of the patient in need
ENDOTRACHEAL INTUBATION of emergency airway management. Although the complication
rates on the regular hospital floor and in the ICU appear to
Table 1.5 is a partial listing of the complications associated be high at around 28% for both locations, they can be mod-
with endotracheal intubation. Factors implicated in the etiol- ified with standardized algorithms as outlined previously. The
ogy of complications include tube size, characteristics of the most frequent complications encountered in these two settings
tube and cuff, trauma during intubation, duration and route are multiple intubation attempts and esophageal intubation in
of intubation, metabolic or nutritional status of the patient, the general hospital units, and severe hypoxemia and hemody-
tube motion, and laryngeal motor activity. namic collapse in the ICU. Presence of acute respiratory failure
During endotracheal intubation, traumatic injury can occur and presence of shock appear to be an independent risk factor
to any anatomic structure from the lips to the trachea. Pos- for the occurrence of complications in the latter setting [55,56].
sible complications include aspiration; damage to teeth and
dental work; corneal abrasions; perforation or laceration of

Complications During Intubation


TA B L E 1 . 5 A variety of cardiovascular complications can accompany in-
COMPLICATIONS OF ENDOTRACHEAL INTUBATION tubation. Ventricular arrhythmias have been reported in 5%
to 10% of intubations. Ventricular tachycardia and ventric-
Complications during intubation ular fibrillation are uncommon but have been reported. Pa-
Spinal cord injury tients with myocardial ischemia are susceptible to ventricular
Excessive delay of cardiopulmonary resuscitation arrhythmias, and lidocaine prophylaxis (100 mg IV bolus) be-
Aspiration fore intubation may be warranted in such individuals. Brad-
Damage to teeth and dental work yarrhythmias can also be observed and are probably caused
Corneal abrasions by stimulation of the laryngeal branches of the vagus nerve.
Perforation or laceration of They may not require therapy but usually respond to IV at-
Pharynx ropine (1 mg IV bolus). Hypotension or hypertension can oc-
Larynx cur during intubation. In the patient with myocardial ischemia,
Trachea short-acting agents to control blood pressure (nitroprusside,
Dislocation of an arytenoid cartilage nicardipine) and heart rate (esmolol) during intubation may be
Passage of endotracheal tube into cranial vault needed.
Epistaxis
Cardiovascular problems
Ventricular premature contractions Complications While the Tube is in Place
Ventricular tachycardia
Bradyarrhythmias Despite adherence to guidelines designed to minimize damage
Hypotension from endotracheal intubation, the tube can damage local struc-
Hypertension tures. Microscopic alterations to the surface of the vocal cords
Hypoxemia can occur within 2 hours after intubation. Evidence of macro-
Complications while tube is in place scopic damage can occur within 6 hours. As might be expected,
Blockage or kinking of tube clinically significant damage typically occurs when intubation
Dislodgment of tube is prolonged. The sudden appearance of blood in tracheal se-
Advancement of tube into a bronchus cretions suggests anterior erosion into overlying vascular struc-
Mechanical damage to any upper airway structure tures, and the appearance of gastric contents suggests poste-
Problems related to mechanical ventilation rior erosion into the esophagus. Both situations require urgent
(see Chapter 58) bronchoscopy, and it is imperative that the mucosa underlying
Complications following extubation the cuff be examined. Other complications include tracheoma-
Immediate complications lacia and stenosis and damage to the larynx. Failure to secure
Laryngospasm the endotracheal tube properly or patient agitation can con-
Aspiration tribute to mechanical damage.
Intermediate and long-term complications Another complication is blockage or kinking of the tube,
Sore throat resulting in compromised ventilation. Placing a bite block in
Ulcerations of lips, mouth, pharynx, or vocal cords the patients mouth can minimize occlusion of the tube caused
Tongue numbness (hypoglossal nerve compression) by the patient biting down on it. Suctioning can usually solve
Laryngitis blockage from secretions, although changing the tube may be
Vocal cord paralysis (unilateral or bilateral) necessary.
Laryngeal edema Unplanned extubation and endobronchial intubation are
Laryngeal ulcerations potentially life threatening. Judicious use of sedatives and
Laryngeal granuloma analgesics and appropriately securing and marking the tube
Vocal cord synechiae should minimize these problems. Daily chest radiographs with
Tracheal stenosis the head always in the same position can be used to assess the
position of the tube. Other complications that occur while the
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Chapter 1: Airway Management and Endotracheal Intubation 15

tube is in position relate to mechanical ventilation (e.g., pneu- consciousness following anesthesia, or (c) sufficient resolution
mothorax) and are discussed in detail in Chapter 58. of the initial indications for intubation.

Complications After Extubation Technique of Extubation


Sore throat occurs after 40% to 100% of intubations. Using a The patient should be alert, lying with the head of the bed
smaller endotracheal tube may decrease the incidence of pos- elevated to at least a 45-degree angle. The posterior pharynx
textubation sore throat and hoarseness. Ulcerations of the lips, must be thoroughly suctioned. The procedure is explained to
mouth, or pharynx can occur and are more common if the ini- the patient. The cuff is deflated, and positive pressure is applied
tial intubation was traumatic. Pressure from the endotracheal to expel any foreign material that has collected above the cuff as
tube can traumatize the hypoglossal nerve, resulting in numb- the tube is withdrawn. Supplemental oxygen is then provided.
ness of the tongue that can persist for 1 to 2 weeks. Irritation In situations in which postextubation difficulties are antici-
of the larynx appears to be due to local mucosal damage and pated, equipment for emergency reintubation should be assem-
occurs in as many as 45% of individuals after extubation. Uni- bled at the bedside. Some clinicians have advocated the leak
lateral or bilateral vocal cord paralysis is an uncommon but test as a means to predict the risk of stridor after extuba-
serious complication following extubation. tion. The utility of this procedure is limited in routine prac-
Some degree of laryngeal edema accompanies almost all en- tice, but for patients with certain risk factors (e.g., traumatic
dotracheal intubations. In adults, this is usually clinically in- intubation, prolonged intubation, and previous accidental ex-
significant. In children, however, even a small amount of edema tubation), a leak volume of greater than 130 mL or 12% of
can compromise the already small subglottic opening. In a new- the tidal volume has a sensitivity and specificity of 85% and
born, 1 mm of laryngeal edema results in a 65% narrowing of 95%, respectively, for the development of postextubation stri-
the airway. Laryngeal ulcerations are commonly observed after dor [57]. Probably the safest means to extubate the patient if
extubation. They are more commonly located at the posterior there are concerns about airway edema or the potential need to
portion of the vocal cords, where the endotracheal tube tends reintubate a patient with a difficult airway is to use an airway
to rub. Ulcerations become increasingly common the longer the exchange catheter. This device is inserted through the endo-
tube is left in place. The incidence of ulceration is decreased by tracheal tube, and then the tube is removed over the catheter.
the use of endotracheal tubes that conform to the anatomic Supplemental oxygen can be provided via the catheter to the
shape of the larynx. Laryngeal granulomas and synechiae of patient, and the catheter can be used as a stent for reintubation
the vocal cords are extremely rare, but these complications can if necessary.
seriously compromise airway patency. Surgical treatment is of- One of the most serious complications of extubation is
ten required to treat these problems. laryngospasm, and it is more likely to occur if the patient is not
A feared late complication of endotracheal intubation is tra- fully conscious. The application of positive pressure can some-
cheal stenosis. This occurs much less frequently now that high- times relieve laryngospasm. If this maneuver is not successful,
volume, low-pressure cuffs are routinely used. Symptoms can a small dose of succinylcholine (by the IV or intramuscular
occur weeks to months after extubation. In mild cases, the pa- route) can be administered. Succinylcholine can cause severe
tient may experience dyspnea or ineffective cough. If the airway hyperkalemia in a variety of clinical settings; therefore, only
is narrowed to less than 5 mm, the patient presents with stridor. clinicians who are experienced with its use should administer
Dilation may provide effective treatment, but in some instances it. Ventilation with a mask and bag unit is needed until the
surgical intervention is necessary. patient has recovered from the succinylcholine.

EXTUBATION Tracheostomy
The decision to extubate a patient is based on (a) a favorable The optimal time of conversion from an endotracheal tube to a
clinical response to a carefully planned regimen of weaning tracheostomy remains controversial. The reader is referred to
from mechanical ventilation (see Chapter 60), (b) recovery of Chapter 12 for details on tracheostomy.

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CHAPTER 2 CENTRAL VENOUS


CATHETERS
JASON LEE-LLACER AND MICHAEL G. SENEFF

The art and science of central venous catheter (CVC) insertion, and it is simply inexcusable for institutions not to fully adapt
maintenance, and management continues to evolve. Increased proven protocols and procedures that have been shown to
emphasis on patient safety and prevention of nosocomial significantly reduce CRI and other catheter complications [1].
complications has focused attention on the impact of CVCs on Patient safety is also the main impetus for increased availability
patient health. Catheter-related infection (CRI), often with a of simulation laboratories [2,3] for operator training in the
resistant organism such as methicillin-resistant Staphylococcal use of portable ultrasound [4,5] to facilitate catheter insertion.
aureus or vancomycin-resistant enterococci (VRE) remains an Insertion of CVCs is a procedure at the crossroads of the
important cause of increased patient morbidity and mortality, controversy of the need for training versus patient safety.
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Chapter 2: Central Venous Catheters 17

Training of physicians in the United States has been guided [6,10]. Ultrasound has been less useful in cannulating the sub-
for years by the mantra see one, do one, teach one, but this clavian vein [11]. The subclavian vein is more difficult to ac-
approach can no longer be defended as the best practice. Dif- cess using ultrasound due to its deeper and posterior location
ferent institutions have developed different solutions, ranging to the clavicle which prevents the transmission of ultrasound
from specially designated catheter teams responsible for waves. The subclavian vein may be accessed at the midpoint of
all hospital-wide catheter insertions, to well equipped simu- the clavicle using a long-axis view or by a supraclavicular ap-
lation laboratories that provide certification of competence proach. Similarly, the infraclavicular axillary vein, which lies a
and which have been shown to reduce subsequent clinical few centimeters lateral to the subclavian vein, can be accessed
complications [2]. with the short-axis ultrasound view [12].
Because of the availability and relatively low cost of portable Because of the success of ultrasound, some experts have ar-
ultrasound units, many nonradiologists have been performing gued for the complete elimination of all nonultrasound-guided
bedside image-guided central venous cannulation. Ultrasound CVC insertions. Although we recognize that even very experi-
guidance allows visualization of the vessel showing its precise enced operators will benefit from ultrasound (if nothing else,
location and patency in real time. It is especially useful for pa- by detection of anatomic variations and thrombosed vessels),
tients with suboptimal body habitus, volume depletion, shock, it is not yet feasible to insist on 100% ultrasound availability.
anatomic deformity, previous cannulation, underlying coagu- We also feel that there are still circumstances where standard
lopathy, and intravenous drug use. The use of ultrasound guid- subclavian catheterization is warranted and that this access site
ance has significantly decreased the failure rate, complication should not be abandoned. Therefore, it is important that one
rate, and the number of attempts in obtaining central venous learns to obtain CVC via landmark techniques.
access and, as a result, has become routine in many centers In this chapter, we review the techniques and complications
[4,6]. Experts all over the world argue that ultrasound guidance of the various routes available for central venous catheteri-
should be viewed as standard of care for all CVC insertions, a zation, and present a strategy for catheter management that
recommendation met with resistance by many clinicians [6,7]. incorporates all of the recent advances.
In 2001, the Agency for Healthcare Research and Quality
Report listed bedside ultrasonography during central venous
access as one of the Top 11 Highly Proven patient safety
practices that are not routinely used in patient care, and it rec- INDICATIONS AND SITE
ommended all CVC insertions be guided by real-time, dynamic SELECTION
ultrasound [8]. The Third Sonography Outcomes Assessment
Program (SOAP-3) trial, a concealed, randomized, controlled Like any medical procedure, CVC has specific indications and
multicenter study, had an odds ratio 53.5 times higher for suc- should be reserved for the patient who has potential to benefit
cess with ultrasound guidance compared with the landmark from it. After determining that CVC is necessary, physicians
technique. It also demonstrated a significantly lower average often proceed with catheterization at the site they are most ex-
number of attempts and average time of catheter placement [9]. perienced with, which might not be the most appropriate route
Given the existing data and recommendations, it appears no in that particular patient. Table 2.1 lists general priorities in
longer defensible to lack an active ultrasound training and uti- site selection for different indications of CVC; the final choice
lization program in the intensive care unit (ICU). Ultrasound of site in a particular patient should vary based on individual
can be used in obtaining central venous access from multi- institutional and operator experiences. In general, we recom-
ple sites, especially the internal jugular and femoral veins (FV) mend that all internal jugular and femoral vein cannulations

TA B L E 2 . 1
INDICATIONS FOR CENTRAL VENOUS CATHETERIZATION (CVC)

Site selection
Indication First Second Third

1. Pulmonary artery catheterization RIJV LSCV LIJV


With coagulopathy IJV FV
With pulmonary compromise or high-level positive end-expiratory pressure (PEEP) RIJV LIJV EJV
2. Total parenteral nutrition (TPN) SCV IJV (tunneled)
Long term (surgically implanted) SCV PICC
3. Acute hemodialysis/plasmapheresis IJV FV
4. Cardiopulmonary arrest FV SCV IJV
5. Emergency transvenous pacemaker RIJV SCV
6. Hypovolemia, inability to perform peripheral IV IJV SCV FV
7. Preoperative preparation IJV SCV AV/PICC
8. General purpose venous access, vasoactive agents, caustic medications, radiologic IJV SCV FV
procedures
With coagulopathy IJV EJV FV
9. Emergency airway management FV SCV IJV
10. Inability to lie supine FV EJV AV/PICC
11. Central venous oxygen saturation monitoring IJV SCV
12. Fluid management of ARDS (CVP monitoring) IJV EJV SCV

AV, antecubital vein; EJV, external jugular vein; FV, femoral vein; IJV, internal jugular vein; L, left; PICC, peripherally inserted central venous catheter;
R, right; SCV, subclavian vein. IJV and FV assume ultrasound guidance. see text for details.
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18 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

be performed under ultrasound guidance. As noted earlier, we drugs and defibrillation, central access should be obtained by
feel the traditional subclavian route offers many advantages for the most experienced operator available with a minimum inter-
central access and should not be abandoned. However, only ex- ruption of CPR. Emergency ultrasound-guided femoral CVC
perienced operators should use the traditional infraclavicular placement has been shown to be slightly faster with fewer com-
approach; others should use ultrasound guidance with a mod- plications than the landmark technique [20].
ified approach that is described later. The placement of CVC is now common in patients with se-
Volume resuscitation alone is not an indication for CVC. vere sepsis, septic shock, or acute respiratory distress syndrome
A 2.5-inch, 16-gauge catheter used to cannulate a peripheral (ARDS), to monitor central venous pressure (CVP) and central
vein can infuse twice the amount of fluid as an 8-inch, 16- venous oxygen saturation (ScvO2 ). Rivers showed a 16% abso-
gauge CVC [13]. However, peripheral vein cannulation can be lute reduction of in-hospital mortality with early goal-directed
impossible in the hypovolemic, shocked individual. Previously, therapy for patients with severe sepsis, which included keeping
we recommended the subclavian vein (SCV) as the most reliable the ScvO2 greater than 70% [21]. Early goal-directed therapy
central site because it remains patent due to its fibrous attach- was subsequently shown to be achievable in real-world set-
ments to the clavicle. But recently, use of real-time ultrasound- tings [22]. For these patients, the relationship between superior
guided CVC placement by direct visualization of the internal vena caval and inferior vena caval oxygen saturations has not
jugular vein (IJV) has increased success rate and decreased com- been definitively elucidated [23]. Likewise, the ARDS network
plications in the shocked or hypovolemic patient [5,6]. reported that CVP monitoring using a CVC is as effective as
Long-term total parenteral nutrition is best administered a pulmonary artery catheter in managing patients with acute
through SCV catheters, which should be inserted by interven- lung injury and ARDS [24]. Because many of these patients
tional radiology or surgically implanted if appropriate. The are on high levels of positive end expiratory pressure (PEEP)
IJV is the preferred site for acute hemodialysis, and the SCV and at high risk for complications from pneumothorax, IJV
should be avoided because of the relatively high incidence of catheterization under ultrasound guidance represents the safest
subclavian stenosis following temporary dialysis, which then approach.
limits options for an AV fistula should long-term dialysis be-
come necessary [14,15]. The FV is also suitable for acute short-
term hemodialysis or plasmapheresis in nonambulatory pa- GENERAL CONSIDERATIONS AND
tients [16].
Emergency trans-venous pacemakers and flow-directed pul- COMPLICATIONS
monary artery catheters are best inserted through the right IJV
because of the direct path to the right ventricle. This route is General considerations for CVC independent of the site of
associated with the fewest catheter tip malpositions. The SCV insertion are the need for signed informed consent, insuring
is an alternative second choice for pulmonary artery catheter- patient comfort and safety, ultrasound preparation, catheter
ization even in many patients with coagulopathy [17]. The tip location, vascular erosions, catheter-associated thrombosis,
left SCV is preferred to the right SV due to a less torturous air and catheter embolism, and the presence of coagulopathy.
route to the heart. The reader is referred to Chapter 4 for ad- Catheter-associated infection is reviewed separately.
ditional information on the insertion and care of pulmonary
artery catheters.
Preoperative CVC is desirable in a wide variety of clinical Informed Consent
situations. One specific indication for preoperative right ven-
tricular catheterization is the patient undergoing a posterior It seems intuitively obvious that a signed informed consent is
craniotomy or cervical laminectomy in the sitting position. mandatory before CVC insertion, but in clinical practice, it is
These patients are at risk for air embolism, and the catheter not that straightforward. CVC insertions in the ICU are ex-
can be used to aspirate air from the right ventricle [18]. Neu- tremely common, occur at all hours of the day, and may be
rosurgery is the only common indication for (but used only crucial for early and appropriate resuscitation and commence-
rarely) antecubital approach, as IJV catheters are in the op- ment of care. Many critically ill patients, especially in urban
erative field and theoretically can obstruct blood return from settings, have no available family members or legal net of kin.
the cranial vault and increase intracranial pressure. Subclavian Obtaining informed consent for these patients may inappro-
catheters are an excellent alternative for preoperative neurosur- priately delay completion of the procedure and impact quality
gical patients if pneumothorax is ruled out prior to induction of care. Because of these considerations, there is no uniform
of general anesthesia. clinical or legal opinion regarding the necessity of individual
Venous access during cardiopulmonary resuscitation war- informed consent prior to all CVC insertions or other ICU pro-
rants special comment. Peripheral vein cannulation in circula- cedures [25]. Some institutions have dealt with this matter by
tory arrest may prove impossible, and circulation times of drugs developing a single general consent form for critical care
administered peripherally are prolonged when compared with that is signed one time for each individual ICU admission and
central injection [19]. Drugs injected through femoral catheters covers all commonly performed bedside procedures. A recent
also have a prolonged circulation time unless the catheter tip review reported that 14% of all surveyed ICUs used such a
is advanced beyond the diaphragm, although the clinical sig- consent form, and overall consent practice varied widely. In
nificance of this is debated. Effective drug administration is general, providers in medical ICUs sought consent for CVC in-
an extremely important element of successful cardiopulmonary sertion more often than providers in surgical ICUs [25]. Given
resuscitation, and all physicians should understand the appro- the lack of agreement on this topic, it seems prudent to make
priate techniques for establishing venous access. It is logical to a few recommendations: (1) Written informed consent should
establish venous access as quickly as possible, either peripher- be obtained prior to all truly elective CVC insertion or other
ally or centrally if qualified personnel are present. Prolonged procedures (2). Whenever possible, competent patients or le-
attempts at arm vein cannulation are not warranted, and un- gal next of kin of incompetent/incapacitated patients should
der these circumstances, the FV is a good alternative. Despite be thoroughly informed of the indications, risks, and benefits
the potential of longer drug circulation times, the FV is rec- of emergency CVC insertion prior to the performance of the
ommended for access in a code situation as cardiopulmonary procedure. If informed consent is not possible prior to CVC
resuscitation (CPR) is interrupted the least with its placement. insertion, then consent should be obtained as soon as possi-
If circulation is not restored after administration of appropriate ble after completion of the procedure. A signed consent form
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Chapter 2: Central Venous Catheters 19

is always preferable, but sometimes not feasible. Oral consent ultrasound plane and appears as single bright echogenic foci on
should be documented in the procedure note by the person ultrasound image. Needle position may be better ascertained
obtaining assent. (3) Emergent CVC placement should not be by slightly moving the needle back and forth displacing the
delayed inappropriately by efforts to obtain consentoral or surrounding soft tissue and possible tenting of vessel wall. It is
written. Patients and family should be told as soon as possible important to note the depth of the vessel on the ultrasound im-
after insertion why the CVC was required. (4) A general con- age to be mindful of how far to penetrate safely with the needle.
sent form that is signed one time as close as possible to ICU The return of blood flow confirms intravascular placement of
admission is a reasonable way to try and inform patients of the the needle tip, and CVC placement may proceed in the usual
benefits/risks of procedures without incurring unnecessary de- fashion. It is good practice to confirm guidewire placement
lays or consumption of clinical time. This form can also serve within the vein as well. The longitudinal approach gives more
as a useful reference for patients and families of all the various information but is more difficult. When using the longitudinal
common procedures that are performed in the ICU. (5) Finally, approach, the plane of the ultrasound and of the needle must
it is good practice to document the practice that is used in the be perfectly aligned and is best for one operator to be holding
ICU Policies and Procedures book and the rationale for it. both probe and needle. First, the vein artery must be visualized
using the transverse view. The probe should then be turned 90
degrees to image just the vein in the long-axis view. Enter the
Patient Comfort and Safety skin just adjacent to the probe at a 45-degree angle. The needle
and needle tip can be directly viewed as it is advanced through
Many patients requiring CVC have an unstable airway or are the vessel. Once in place, advance the guidewire under direct
hemodynamically unstable. These considerations should im- visualization.
pact preparation and choice of site. For example, many pa-
tients are claustrophobic and will not tolerate their face being
covered; others who are dyspneic will not tolerate lying flat. Mobile Catheter Cart
In our experience, significant physiologic decompensation or
even code blues may occur during CVC placement because Availability of a mobile catheter cart that contains all neces-
the operator is focused on establishing access and/or interprets sary supplies and that can be wheeled to the patients bedside
the silent patient as one who is having no problems. Every is good practice and likely reduces overall catheter infection
patient should be specifically assessed prior to CVC regarding rate by decreasing breaks in sterile technique [26]. In our expe-
their positioning, airway, and hemodynamic stability. On more rience, the mobile cart is also an excellent way to standardize
than one occasion, we have placed a femoral catheter because all catheter insertions, facilitate communication of procedural
a patient could not lie flat or needed emergency venous access tasks (such as use of a time-out), and allow for staff to timely
for endotracheal intubation. Once the patient is stabilized, the complete mandatory forms.
appropriate site/catheter can then be inserted under less unsta-
ble/rigorous conditions.
Catheter Tip Location
Ultrasound Preparation Catheter tip location is a very important consideration in CVC
placement. The ideal location for the catheter tip is the dis-
Ultrasound enables immediate identification of anatomic varia- tal innominate or proximal superior vena cava (SVC), 3 to
tion, confirmation of vessel patency, and direct visualization of 5 cm proximal to the cavalatrial junction. Positioning of the
the needle entering the vessel. The difference between vein and catheter tip within the right atrium or right ventricle should
artery can be determined by compressibility, shape, Doppler be avoided. Cardiac tamponade secondary to catheter tip per-
flow, and increasing size with the Valsalva or other maneuvers. foration of the cardiac wall is uncommon, but two thirds of
Veins are usually ovoid in shape, completely compressible, and patients suffering this complication die [27]. Perforation likely
have thin walls; in contrast, arteries are circular, difficult to results from vessel wall damage from infused solutions com-
compress, and have thick walls. bined with catheter tip migration that occurs from the motion
When performing ultrasound, the same general technique is of the beating heart as well as patient arm and neck movements.
followed regardless of the site of puncture [6]. A quick, nonster- Migration of catheter tips can be impressive: 5 to 10 cm with
ile survey should be made with the vascular probe to quickly antecubital catheters and 1 to 5 cm with IJV or SCV catheters
identify the presence of a suitable vein for catheterization. After [28,29]. Other complications from intracardiac catheter tip po-
sterile preparation of the patient and site, the vascular probe sition include provocation of arrhythmias from mechanical irri-
should be used with a sterile probe cover kit. This kit contains tation and infusion of caustic medications or unwarmed blood
a sterile sleeve, sterile jelly, and rubber bands. To apply the [30].
sterile sleeve, have an assistant place nonsterile jelly inside the Correct placement of the catheter tip is relatively simple,
sleeve and then place probe in the sleeve. Extend the sleeve beginning with an appreciation of anatomy. The cavalatrial
over the cord and fasten the sleeve with rubber bands. One junction is approximately 16 to 18 cm from right-sided skin
band should be fastened toward the head of the probe to en- punctures and 19 to 21 cm from left-sided insertions and is rel-
sure the jelly remains in place for optimal imaging. Sterile jelly atively independent of patient gender and body habitus [31,32].
is then applied to the tip of probe on the outside of sleeve. Insertion of a standard 20-cm triple-lumen catheter to its full
The target vessels may be visualized using a transverse or length frequently places the tip within the heart, especially fol-
longitudinal view. The transverse approach is technically eas- lowing right-sided insertions. A chest radiograph should be
ier than the longitudinal approach and is the best approach for obtained following every initial CVC insertion to ascertain
beginners. The transverse view allows identification of the tar- catheter tip location and to detect complications. The right
get vein in relation to the artery, which helps decrease risk of tracheobronchial angle is the most reliable landmark on plain
unintentional puncture of the artery. Once identified, the vein film chest X-ray for the upper margin of the SVC, and is always
should be centered underneath the probe. An 18-gauge needle at least 2.9 cm above the cavalatrial junction. The catheter tip
should slowly be advanced with the skin puncture site proxi- should lie about 1 cm below this landmark, and above the
mal to the probe, so that vessel puncture is directly visualized. right upper cardiac silhouette to ensure placement outside of
With this approach, the needle traverses diagonally across the the pericardium [33].
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20 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

cannulation under ultrasound guidance has proven to be very


Vascular Erosions safe, while the FV offers a viable alternative for general-purpose
venous access. In nonemergent patients, peripherally inserted
Large-vessel perforations secondary to CVCs are uncommon central venous catheters (PICC) can be used.
and often not immediately recognized. Vessel perforation typ-
ically occurs 1 to 7 days after catheter insertion. Patients usu-
ally present with sudden onset of dyspnea and often with new
pleural effusions on chest radiograph [34]. Catheter stiffness, Thrombosis
position of the tip within the vessel, and the site of insertion
are important factors causing vessel perforation. The relative Catheter-related thrombosis is very common but usually of
importance of these variables is unknown. Repeated irritation little clinical significance. The spectrum of thrombotic compli-
of the vessel wall by a stiff catheter tip or infusion of hyperos- cations includes a fibrin sleeve surrounding the catheter from
molar solutions may be the initiating event. Vascular erosions its point of entry into the vein distal to the tip, mural thrombus,
are more common with left IJV and EJV catheters, because for a clot that forms on the wall of the vein secondary to mechani-
anatomical reasons the catheter tip is more likely to be posi- cal or chemical irritation, or occlusive thrombus, which blocks
tioned laterally under tension against the SVC wall [35]. Posi- flow and may result in collateral formation. All of these lesions
tioning of the catheter tip within the vein parallel to the vessel are usually clinically silent; therefore, studies that do not use
wall must be confirmed on chest radiograph. Free aspiration venography or color flow Doppler imaging to confirm the di-
of blood from one of the catheter ports is not always sufficient agnosis underestimate its incidence. Using venography, fibrin
to rule out a vascular perforation. sleeve formation can be documented in a majority of catheters,
mural thrombi in 10% to 30%, and occlusive thrombi in 0%
to 10% [4045]. In contrast, clinical symptoms of thrombosis
occur in only 0% to 3% of patients. The incidence of thrombo-
Air and Catheter Embolism sis probably increases with duration of catheterization but does
not appear reliably related to the site of insertion. However, the
Significant air and catheter embolism are rare and preventable clinical importance of femoral vein catheter-associated throm-
complications of CVC. Catheter embolism can occur at the bosis compared to upper extremity thrombosis caused by IJ
time of insertion when a catheter-through- or over-needle tech- and SCV catheters is unknown [46]. The presence of catheter-
nique is used and the operator withdraws the catheter without associated thrombosis is also associated with a higher incidence
simultaneously retracting the needle. It more commonly occurs of infection [47].
with antecubital or femoral catheters after insertion, because
they are prone to breakage when the agitated patient vigorously
bends an arm or leg. Prevention, recognition, and management
of catheter embolism are covered in detail elsewhere [36]. ROUTES OF CENTRAL VENOUS
Air embolism is of greater clinical importance, often goes CANNULATION
undiagnosed, and may prove fatal. This complication is totally
preventable with compulsive attention to proper catheter inser-
tion and maintenance. Factors resulting in air embolism dur- Antecubital Approach
ing insertion are well known, and methods to increase venous
The antecubital veins are used in the ICU for CVC with PICC
pressure, such as use of the Trendelenburg position, should
and midline catheters. Use of PICCs in critically ill adults is be-
not be forgotten. Catheter disconnection and passage of air
coming increasingly important. Specialized nursing teams are
through a patent tract after catheter removal are more com-
now able to insert PICCs at beside with use of real-time ultra-
mon causes of catheter-associated air embolism. An air embo-
sonography and sterile technique thereby increasing safety and
lus should be suspected in any patient with an indwelling or
reducing the potential for infection. There are now triple lu-
recently discontinued CVC who develops sudden unexplained
men catheters that may be inserted with this approach. PICCs
hypoxemia or cardiovascular collapse, often after being moved
may be useful in ICU patients undergoing neurosurgery, with
or transferred out of bed. A characteristic mill wheel sound may
coagulopathy, or in the rehabilitative phase of critical illness
be auscultated over the precordium. Treatment involves plac-
for which general purpose central venous access is required for
ing the patient in the left lateral decubitus position and using
parenteral nutrition or long-term medication access (Table 2.1)
the catheter to aspirate air from the right ventricle. Hyper-
[48,49]. Although many hospitals have a designated PICC
baric oxygen therapy to reduce bubble size has a controversial
insertion team, they may have significant work hour limitations
role in treatment [37]. The best treatment is prevention which
that delay insertion of catheters and result in significant delays
can be effectively achieved through comprehensive nursing and
in delivery of care or throughput. For that reason, we believe
physician-in-training educational modules and proper supervi-
intensivists should be familiar with the antecubital route, and
sion of inexperienced operators [38].
as a result, the technique of percutaneous insertion of catheters
using the basilic vein is described later.
Coagulopathy Anatomy
Central venous access in the patient with a bleeding diathesis The basilic vein is preferred for CVC because it is almost always
can be problematic. The SCV and IJV routes have increased of substantial size and the anatomy is predictable. The basilic
risks in the presence of coagulopathy, but the true risk is fre- vein provides an unimpeded path to the central venous circula-
quently overestimated and it is not known at what degree of tion via the axillary vein [50,51]. The basilic vein is formed at
abnormality it becomes unacceptable. A coagulopathy is gener- the ulnar aspect of the dorsal venous network of the hand. It
ally defined as an international normalized ratio (INR) greater may be found in the medial part of the antecubital fossa, where
than 1.5 or platelet count less than 50,000. Although it is it is usually joined by the median basilic vein. It then ascends
clear that safe venipuncture is possible (even with the subcla- in the groove between the biceps brachii and pronator teres on
vian approach) with greater degrees of coagulopathy [39], the the medial aspect of the arm to perforate the deep fascia distal
literature is also fraught with case reports of serious hemor- to the midportion of the arm, where it joins the brachial vein
rhagic complications. In patients with severe coagulopathy, IJV to become the axillary vein.
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Chapter 2: Central Venous Catheters 21

Technique of Cannulation the catheter cannot be advanced easily, another site should be
chosen.
Several kits are available for antecubital CVC. The PICC and
midline catheters are made of silicone or polyurethane and,
depending on catheter stiffness and size, are usually placed Success Rate and Complications
through an introducer. The method described below is for a Using the above-mentioned technique, PICC catheters have a
PICC inserted through a tear-away introducer. 75% to 95% successful placement rate. Overall, PICCs ap-
The success rates from either arm are comparable, though pear to be at least as safe as CVCs, but important compli-
the catheter must traverse a greater distance from the left. With cations include sterile phlebitis, thrombosis (especially of the
the patients arm at his or her side, the antecubital fossa is SCV and IJV), infection, limb edema, and pericardial tampon-
prepared with chlorhexidine and draped using maximum bar- ade. Phlebitis may be more common with antecubital CVCs,
rier precautions (mask, cap and sterile gown, gloves and large probably due to less blood flow in these veins as well as the
drape covering the patient). A tourniquet is placed proximally proximity of the venipuncture site to the skin [52,53]. The risk
by an assistant and a portable ultrasound device used to iden- of pericardial tamponade may also be increased if the catheter
tify the basilic or its main branches. A vein can be distinguished tip is inserted too deep because of greater catheter tip migra-
from an artery by visualizing compressibility, color flow, and tion occurring with arm movements [54]. Complications are
Doppler flow (Fig. 2.1). After a time-out and administration minimized by strict adherence to recommended techniques for
of local anesthesia subcutaneously, venipuncture is performed catheter placement and care.
with the thin wall entry needle a few centimeters proximal
to the antecubital crease to avoid catheter breakage and em-
bolism. When free backflow of venous blood is confirmed, the
tourniquet is released and the guidewire carefully threaded into Internal Jugular Approach
the vein for a distance of 15 to 20 cm. Leaving the guidewire in
place, the thin-wall needle is withdrawn and the puncture site The IJV has been used for venous access in pediatric and adult
enlarged with a scalpel blade. The sheath-introducer assem- patients for many years but its use in some circumstances has
bly is threaded over the guidewire with a twisting motion, and been limited by a relatively lower rate of success due to its com-
the guidewire removed. Next, leaving the sheath in place, the pressibility and propensity to collapse in hypovolemic condi-
dilator is removed, and the introducer is now ready for PICC tions. In our opinion, ultrasound has had its greatest impact by
insertion. The length of insertion is estimated by measuring improving the efficiency of IJV cannulation, since real-time di-
the distance along the predicted vein path from the venipunc- rect visualization of the vein is easily obtained. This minimizes
ture site to the manubriosternal junction, using the measuring the impact of hypovolemia or anatomical variations on overall
tape provided in the kit. The PICC is typically supplied with success, and has rendered the need for EJV catheterization al-
an inner obturator that provides stiffness for insertion. The most extinct. Furthermore, under ultrasound guidance, the cen-
PICC is trimmed to the desired length and flushed with saline tral approach is almost always used, and as a result, we will no
and the obturator is inserted into the PICC up to the tip. The longer review the anterior or posterior approaches. In general,
PICC/obturator assembly is inserted through the introducer to these techniques will differ only in the point of skin puncture
the appropriate distance, the introducer peeled away, and the (Fig. 2.2), and readers are referred to previous editions of this
obturator removed. The PICC is secured in place and a chest text for a thorough description of these approaches.
X-ray obtained to determine tip position.
If resistance to advancing the PICC is met, options are lim- Anatomy
ited. Techniques such as abducting the arm are of limited value.
The IJV emerges from the base of the skull through the jugular
If a catheter-through- or over-needle device has been used, the
foramen and enters the carotid sheath dorsally with the inter-
catheter must never be withdrawn without simultaneously re-
nal carotid artery (ICA). It then courses posterolaterally to the
tracting the needle to avoid catheter shearing and embolism. If
artery and runs beneath the sternocleidomastoid (SCM) mus-
cle. The vein lies medial to the anterior portion of the SCM
muscle superiorly and then runs beneath the triangle formed
by the two heads of the muscle in its medial portion before
entering the SCV near the medial border of the anterior sca-
lene muscle at the sternal border of the clavicle. The junction
of the right IJV (which averages 2 to 3 cm in diameter) with
the right SCV forming the innominate vein follows a straight
path to the SVC. As a result, catheter malposition and looping
of the catheter inserted through the right IJV are unusual. In
contrast, a catheter passed through the left IJV must negotiate
a sharp turn at the left jugulosubclavian junction, which re-
sults in a greater percentage of catheter malpositions [55]. This
sharp turn may also produce tension and torque at the catheter
tip, resulting in a higher incidence of vessel erosion.
Knowledge of the structures neighboring the IJV is essential
as they may be compromised by a misdirected needle. The ICA
runs medial to the IJV but, rarely, may lie directly posterior
or, rarely, anterior. Behind the ICA, just outside the sheath, lie
the stellate ganglion and the cervical sympathetic trunk. The
dome of the pleura, which is higher on the left, lies caudal to the
junction of the IJV and SCV. Posteriorly, at the root of the neck,
course the phrenic and vagus nerves. The thoracic duct lies
posterior to the left IJV and enters the superior margin of the
FIGURE 2.1. Ultrasound view of the basilica vein at the antecubital SCV near the jugulosubclavian junction. The right lymphatic
fossa. duct has the same anatomical relationship but is much smaller,
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22 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

A
B

C D
FIGURE 2.2. Surface anatomy and various approaches to cannulation of the internal jugular vein.
A: Surface anatomy. B: Anterior approach. C: Central approach. D: Posterior approach. The external
jugular vein is also shown.

and chylous effusions typically occur only with left-sided IJV The IJV is usually readily identified by ultrasound (Fig. 2.3),
cannulations. and if the anatomy is normal and the IJV of substantial size,
use of a finder needle is not required. The operator can directly
visualize the needle entering the vein, and then proceed with
Technique of Cannulation insertion of the guidewire and catheter as described later. It
With careful preparation of equipment and attention to patient is important not to be mesmerized or to have a false sense
comfort and safety as described earlier, the patient is placed in a of confidence because ultrasound is being used. Always follow
15-degree Trendelenburg position to distend the vein and min- standard catheterization technique and always confirm (using
imize the risk of air embolism. The head is turned gently to multiple techniques) venous puncture. For example, it is good
the contralateral side. The surface anatomy is identified, espe- practice to document that the needle or short cannula is in the
cially the angle of the mandible, the two heads of the SCM, the IJV through the use of manometry or to visualize the guidewire
clavicle, the EJV, and the trachea (Fig. 2.2). We recommend pre- within the vein by using ultrasound before proceeding with
liminary ultrasound examination of the IJV before skin prepa- catheter insertion.
ration to quickly identify anatomical variations and suitability If ultrasound is unavailable, skin puncture is at the apex
for catheterization. The probe should initially be placed in the of the triangle formed by the two muscle bellies of the SCM
center of the triangle formed by the clavicle and two heads of and the clavicle. The ICA pulsation is usually felt 1 to 2 cm
the SCM. If on the ultrasound the IJV is very small, throm- medial to this point, beneath or just medial to the sternal head
bosed, or there is a significant anatomical variant, it is best to of the SCM. The skin at the apex of the triangle is infiltrated
choose another site since successful cannulation is directly de- with 1% lidocaine using the smallest needle available. Use of a
pendent on cross-sectional luminal size of the vessel. The neck small-bore finder needle to locate the IJV should prevent unin-
is then prepared with chlorhexidine and fully draped, using tentional ICA puncture and unnecessary probing with a larger
maximum barrier precautions. Before the procedure is begun, bore needle. To avoid collapsing the IJV, the operator should
a time-out is performed. maintain minimal to no pressure on the ICA with the left hand
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Chapter 2: Central Venous Catheters 23

perforation. Furthermore, if the patient has an IVC filter in


place, the guidewire can become entangled in the filter. Occa-
sionally, the guidewire does not pass easily beyond the tip of
the thin-wall needle. The guidewire should then be withdrawn,
the syringe attached, and free backflow of blood reestablished
and maintained while the syringe and needle are brought to a
more parallel plane with the vein. The guidewire should then
pass easily. If resistance is still encountered, rotation of the
guidewire during insertion often allows passage, but extensive
manipulation and force lead only to complications.
With the guidewire in place, a scalpel is used to make two
90-degree stab incisions at the skin entry site to facilitate pas-
sage of the 7-Fr vessel dilator. The dilator is inserted down
the wire to the hub, ensuring that control and sterility of the
guidewire is not compromised. The dilator is then withdrawn
and pressure used at the puncture site to control oozing and
prevent air embolism down the needle tract. The proximal and
middle lumens of a triple-lumen catheter are flushed with saline
and capped. The catheter is then inserted over the guidewire,
ensuring that the operator has control of the guidewire, either
proximal or distal to the catheter, at all times to avoid intravas-
cular loss of the wire. The catheter is then advanced 15 to
17 cm (17 to 19 cm for left IJV) into the vein, the guidewire
withdrawn, and the distal lumen capped. The catheter is su-
tured securely to limit tip migration and bandaged in a stan-
FIGURE 2.3. Ultrasound appearance of the right internal jugular vein dard manner. A chest radiograph should be obtained to detect
and normal relationship with the internal carotid artery. complications and tip location.

Success Rates and Complications


and insert the finder needle with the right hand at the apex
of the triangle at a 45-degree angle with the frontal plane, di- Nonultrasound-guided IJV catheterization is associated with
rected at the ipsilateral nipple. The needle is advanced steadily a high rate of successful catheter placement. Elective proce-
with constant negative pressure in the syringe, and venipunc- dures are successful more than 90% of the time, generally
ture occurs within 1 to 5 cm. If venipuncture does not occur within the first three attempts, and catheter malposition is rare.
on the initial attempt, negative pressure should be maintained Use of ultrasound clearly improves the success rate, decreases
and the needle slowly withdrawn, as often, the needle will the number of attempts and complications, avoids unnecessary
compress the vein on advancement and penetrate the back procedures by identifying unsuitable anatomy, and minimally
wall without blood return. Once the needle is pulled back past impacts insertion time. Emergent IJV catheterization is less suc-
the posterior wall of the vessel, it achieves free flow of blood cessful and is not the preferred technique during airway emer-
from the vessel. If the first attempt is unsuccessful, the operator gencies or other situations that may make it difficult to identify
should reassess patient position, landmarks, and techniques to landmarks in the neck.
ensure that he or she is not doing anything to decrease IJV The incidence and types of complications are similar regard-
lumen size (see later). Subsequent attempts may be directed less of the approach. Operator inexperience appears to increase
slightly laterally or medially to the initial direction, as long the number of complications, but to an undefined extent, and
as the ICA is not entered. If venipuncture does not occur af- probably does not have as great an impact as it does on the
ter three to five attempts, further attempts are unlikely to be incidence of pneumothorax in subclavian venipuncture [60].
successful and only increase complications [5658]. The overall incidence of complications in IJV catheteriza-
When venipuncture has occurred with the finder needle, the tion (without ultrasound guidance) is 0.1% to 4.2%. Impor-
operator can either withdraw the finder needle and introduce tant complications include ICA puncture, pneumothorax, ves-
the large-bore needle in the identical plane or leave the finder sel erosion, thrombosis, and infection. Although the impact of
needle in place and introduce the larger needle directly superior ultrasound use on other complications has not been conclu-
to it. Leaving the finder needle in place has been shown to facil- sively demonstrated, it has been shown to significantly reduce
itate successful puncture with the introducer needle [59]. Many the number of attempts and the incidence of arterial puncture,
kits provide both an 18-gauge thin-wall needle through which a which is by far the most common complication [6]. In the ab-
guidewire can be directly introduced and a 16-gauge catheter- sence of a bleeding diathesis, arterial punctures are usually be-
over-needle device. With the latter apparatus, the catheter is nign and are managed conservatively by applying local pressure
threaded over the needle into the vein, the needle withdrawn, for 10 minutes. Even in the absence of clotting abnormalities,
and the guidewire inserted through the catheter. Both tech- a sizable hematoma may form, frequently preventing further
niques are effective; the choice is strictly a matter of operator catheterization attempts or, rarely, exerting pressure on vital
preference. Regardless of which large-bore needle is used, once neck structures [61,62]. Unrecognized arterial puncture can
venipuncture has occurred the syringe is removed after ensur- lead to catheterization of the ICA with a large-bore catheter
ing that the backflow of blood is not pulsatile and the hub is or introducer and can have disastrous consequences, especially
then occluded with a finger to prevent air embolism or excessive if heparin is subsequently administered [63]. Management of
bleeding. The guidewire, with the J-tip oriented appropriately, carotid cannulation with a large-bore catheter, such as a 7-Fr in-
is then inserted and should pass freely up to 20 cm, at which troducer, is controversial. Options include pulling the catheter
point the thin-wall needle or catheter is withdrawn. The ten- and applying pressure, percutaneous closure devices, internal
dency to insert the guidewire deeper than 15 to 20 cm should stent grafting, or surgical repair [64,65]. Some experts ad-
be avoided, as it is the most common cause of ventricular ar- vise administration of anticoagulants to prevent thromboem-
rhythmias during insertion and also poses a risk for cardiac bolic complications, whereas others advise the opposite. Our
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24 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

approach is to remove small bore catheters and avoid hep- vanced in the axis of the vein at 20 degrees to the frontal plane.
arinization if possible, as hemorrhage appears to be a greater The EJV may be more difficult to cannulate than expected be-
risk than thromboembolism. For larger bore catheters and cause of its propensity to roll and displace rather than puncture
complicated cases, we involve interventional radiology and vas- in response to the advancing needle. A firm, quick thrust is often
cular surgery before removal, and individualize the manage- required to effect venipuncture. When free backflow of blood
ment based on the circumstances. is established, the needle tip is advanced a few millimeters fur-
Pneumothorax, which may be complicated by blood, in- ther into the vein and the catheter is threaded over the needle.
fusion of intravenous fluid, or tension, is considered an un- The catheter may not thread its entire length because of valves,
usual adverse consequence of IJV cannulation; however, it has tortuosity, or the SCV junction, but should be advanced at least
an incidence of 1.3% in a large meta-analysis, statistically the 3 to 5 cm to secure venous access. The syringe and needle can
same as 1.5% found for subclavian puncture [66]. It usually then be removed and the guidewire, J-tip first, threaded up to
results from a skin puncture too close to the clavicle or, rarely, 20 cm and the catheter removed. Manipulation and rotation
from other causes. Logically, ultrasound should decrease or of the guidewire, especially when it reaches the SCV junction,
even eliminate pneumothorax as a complication during IJV may be necessary but should not be excessive. Various arm and
catheterization. head movements are advocated to facilitate guidewire passage;
An extraordinary number of case reports indicate that any abduction of the ipsilateral arm and anteriorposterior pressure
complication from IJV catheterization is possible, even the in- exerted on the clavicle may be helpful. Once the guidewire has
trathecal insertion of a pulmonary artery catheter [67]. In real- advanced 20 cm, two 90-degree skin stabs are made with a
ity, the IJ route is reliable, with a low incidence of major compli- scalpel, and the vein dilator inserted to its hub, maintaining
cations. Operator experience is not as important a factor as in control of the guidewire. The triple-lumen catheter is then in-
SCV catheterization; the incidence of catheter tip malposition serted an appropriate length (16 to 17 cm on the right, 18 to
is low, and patient acceptance is high. It is best suited for acute, 20 cm on the left). The guidewire is withdrawn, the catheter
short-term hemodialysis and for elective or urgent catheteriza- bandaged, and a chest radiograph obtained to screen for com-
tions in volume-replete patients, especially pulmonary artery plications and tip placement.
catheterizations and insertion of temporary transvenous pace-
makers. It is not the preferred site during airway emergencies, Success Rates and Complications
for parenteral nutrition, or for long-term catheterization be-
Central venous catheterization via the EJV is successful in 80%
cause infectious complications are higher with IJV compared
of patients (range 75% to 95%) [68,69]. Inability to perform
with SCV catheterizations.
venipuncture accounts for up to 10% of failures [70,71] and the
remainders are a result of catheter tip malpositioning. Failure
to position the catheter tip is usually due to inability to ne-
External Jugular Vein Approach gotiate the EJVSCV junction, loop formation, or retrograde
passage down the ipsilateral arm. Serious complications aris-
The EJV is now rarely used for CVC, but in selected cases, it
ing from the EJV approach are rare and almost always asso-
remains an excellent alternative. The main advantages to the
ciated with catheter maintenance rather than venipuncture. A
EJV route for CVC are that it is part of the surface anatomy, the
local hematoma forms in 1% to 5% of patients at the time of
risk of hemorrhage is low even in the presence of coagulopathy,
venipuncture [72] but has little consequence unless it distorts
and the risk of pneumothorax is all but eliminated. The main
the anatomy leading to catheterization failure. External jugular
disadvantage is the unpredictability of passage of the catheter
venipuncture is safe in the presence of coagulopathy. Infectious,
to the central compartment.
thrombotic, and other mechanical complications are no more
frequent than with other central routes.
Anatomy
The EJV is formed anterior and caudal to the ear at the angle
of the mandible by the union of the posterior auricular and Femoral Vein Approach
retromandibular veins (Fig. 2.2). It courses obliquely across
the anterior surface of the SCM, then pierces the deep fascia The FV has many practical advantages for CVC; it is directly
just posterior to the SCM and joins the SCV behind the medial compressible, it is remote from the airway and pleura, the tech-
third of the clavicle. In 5% to 15% of patients, the EJV is nique is relatively simple, and the Trendelenburg position is not
not a distinct structure but a venous plexus, in which case it required during insertion. During the mid-1950s, percutaneous
may receive the ipsilateral cephalic vein. The EJV varies in size catheterization of the IVC via a femoral vein approach became
and contains valves throughout its course. Its junction with the popular until 1959 when Moncrief [73] and Bansmer et al.
SCV may be at a severe, narrow angle that can be difficult for [74] reported a high incidence of complications, especially in-
a catheter to traverse [50,51]. fection and thrombosis, after which, it was largely abandoned.
In the subsequent two decades, FV cannulation was restricted
Technique to specialized clinical situations. Interest in short-term (<48
hour) FV catheterization was renewed by positive experiences
The EJV should be cannulated using the 16-gauge catheter-
during the Vietnam conflict and with patients in the emergency
over-needle, since guidewire manipulations are often necessary,
department [75]. Some reports on long-term FV catheteriza-
and secure venous access with a catheter is preferable. The pa-
tion [76] suggest an overall complication rate no higher than
tient is placed in a comfortable supine position with arms to the
that with other routes, although deep vein thrombosis remains
side and head turned slightly to the contralateral side. The right
a legitimate concern. Furthermore, Centers for Disease Control
EJV should be chosen for the initial attempt and can be identi-
and Prevention (CDC) guidelines for the prevention of catheter-
fied where it courses over the anterior portion of the clavicular
related bloodstream infection recommend against the use of the
belly of the SCM. After skin preparation with chlorhexidine,
femoral site for catheterization if possible [77].
use of maximum barrier precautions, administration of local
anesthesia subcutaneously and a time-out, venipuncture is per-
formed with the 16-gauge catheter-over-needle using the left
Anatomy
index finger and thumb to distend and anchor the vein. Skin The FV (Fig. 2.4A) is a direct continuation of the popliteal vein
puncture should be well above the clavicle and the needle ad- and becomes the external iliac vein at the inguinal ligament. At
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Chapter 2: Central Venous Catheters 25

B
A

FIGURE 2.4. A: Anatomy of the femoral vein. B: Ultrasound appearance of femoral vein and artery.

the inguinal ligament, the FV lies within the femoral sheath a pubic tubercle is divided into three equal segments. The femoral
few centimeters from the skin surface. The FV lies medial to the artery is usually found where the medial segment meets the
femoral artery, which in turn lies medial to the femoral branch two lateral ones, and the FV lies 1 to 1.5 cm medial. Follow-
of the genitofemoral nerve. The medial compartment contains ing a time-out, an 18-gauge thin-wall needle is inserted at this
lymphatic channels and Cloquets node. The external iliac vein point, 2 to 3 cm inferior to the inguinal ligament, ensuring that
courses cephalad from the inguinal ligament along the anterior venipuncture occurs caudal to the inguinal ligament, which
surface of the iliopsoas muscle to join its counterpart from the minimizes the risk of retroperitoneal hematoma in the event of
other leg and form the (IVC) anterior to and to the right of arterial puncture. While maintaining constant back pressure
the fifth lumbar vertebra. Using ultrasound, the femoral vein on the syringe, the needle, tip pointed cephalad, is advanced
can be readily identified by placing the probe a few centime- at a 45-degree angle to the frontal plane. Insertion of the nee-
ters caudal to the inguinal ligament, just medial to the arterial dle to its hub is sometimes required in obese patients. Blood
pulsation (Fig. 2.4B). return may not occur until slow withdrawal. If the initial at-
tempt is unsuccessful, landmarks should be reevaluated and
subsequent attempts oriented slightly more medial or lateral.
Technique A common error is to direct the needle tip too medially, toward
Femoral vein cannulation is the easiest of all central venous the umbilicus. The femoral vessels lie in the sagittal plane at the
procedures to learn and perform. Either side is suitable, and inguinal ligament (Fig. 2.4), and the needle should be directed
the side chosen is based on operator convenience. Ultrasound accordingly. If unintentional arterial puncture occurs, pressure
guidance is not usually required but for elective situations, we is applied for 5 to 10 minutes.
believe it is optimal practice. Ultrasound confirms the anatomy, When venous blood return is established, the syringe angle
identifies the depth needed for venipuncture, rules out preexist- is depressed slightly and free aspiration of blood reconfirmed.
ing thrombosis, and should not unduly delay time to catheter- The syringe is removed, ensuring that blood return is not pul-
ization. It may be particularly useful in the obese [21]. The pa- satile. The guidewire should pass easily and never forced, al-
tient is placed in the supine position (if tolerated) with the leg though rotation and minor manipulation are sometimes re-
extended and slightly abducted at the hip. Excessive hair should quired. The needle is then withdrawn, two scalpel blade stab
be clipped with scissors and the skin prepped with chlorhex- incisions made at 90 degrees at the guidewire insertion site,
idine. Maximum barrier precautions should be used. The FV and the vein dilator inserted over the wire to the hub. The dila-
lies 1 to 1.5 cm medial to the arterial pulsation, and the over- tor is then withdrawn and a catheter appropriate to clinical
lying skin is infiltrated with 1% lidocaine. In a patient without requirements inserted, taking care never to lose control of the
femoral artery pulsations, the FV can be located by dividing guidewire. The catheter is secured with a suture and bandage
the distance between the anterior superior iliac spine and the applied.
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26 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

Success Rate and Complications thrombosis occurs with similar frequency as with IJ and SV
catheters, but it may be more clinically relevant.
FV catheterization is successful in 90% to 95% of patients,
including those in shock or cardiopulmonary arrest [77,78].
Unsuccessful catheterizations are usually a result of venipunc-
ture failure, hematoma formation, or inability to advance the
guidewire into the vein. Operator inexperience may increase Subclavian Vein Approach
the number of attempts and complication rate but does not
This route has been used for central venous access for many
appear to significantly decrease the overall success rate.
years and is associated with the most controversy, largely be-
Three complications occur regularly with FV catheteriza-
cause of the relatively high incidence of pneumothorax and the
tion: arterial puncture with or without local bleeding, infection,
occasional mortality associated with it. With the added safety
and thromboembolic events. Other reported complications are
of ultrasound-guided IJV catheterization, there has been some
rare and include scrotal hemorrhage, right lower quadrant
debate about abandonment of landmark guided SCV catheter-
bowel perforation, retroperitoneal hemorrhage, puncture of
ization. Ultrasound guidance is possible with the SCV, but it
the kidney, and perforation of IVC tributaries. These com-
is more technically demanding and may require a different site
plications occur when skin puncture sites are cephalad to the
for venipuncture [12]. Given these factors, we still believe the
inguinal ligament or when long catheters are threaded into the
SCV is a valuable alternative in certain situations for experi-
FV.
enced operators, who should have a pneumothorax rate well
Femoral artery puncture occurs in 5% to 10% of
under 1%. Inexperienced operators have a far greater rate of
adults. Most arterial punctures are uncomplicated, but major
pneumothorax; therefore, in settings where relatively inexperi-
hematomas may form in 1% of patients, especially in the pres-
enced physicians perform the majority of CVC, the SCV should
ence of anticoagulants, fibrinolytics, or antithrombotic agents.
be used more selectively or perhaps, not at all. The advantages
As is the case with other routes, ultrasound should essentially
of this route include consistent identifiable landmarks, easier
eliminate this complication. Even in the presence of coagu-
long-term catheter maintenance with a comparably lower rate
lopathy, arterial puncture with the 18-gauge thin-wall needle
of infection, and relatively high patient comfort. Assuming an
is usually of minor consequence, but there is a potential for
experienced operator is available, the SCV is the preferred site
life-threatening thigh or retroperitoneal hemorrhage [79]. Ar-
for CVC in patients with hypovolemia, for long-term total par-
teriovenous fistula and pseudoaneurysm are rare chronic com-
enteral nutrition (TPN), and in patients with elevated intracra-
plications of arterial puncture; the former is more likely to oc-
nial pressure who require hemodynamic monitoring. It should
cur when both femoral vessels on the same side are cannulated
not be considered the primary choice in the presence of throm-
concurrently [80].
bocytopenia (platelets <50,000), for acute hemodialysis, or in
Infectious complications with FV catheters are probably
patients with high PEEP (i.e., >12 cm H2 O).
more frequent than SCV catheters but comparable to IJV
catheters [8183]. Modern series involving both short- and
long-term FV catheterization in adults and children have re-
ported significant CRI rates of about 5% or less [77,84]. Fur-
Anatomy
ther evidence that the inguinal site is not inherently dirty is The SCV is a direct continuation of the axillary vein, begin-
provided by experience with femoral artery catheters, which ning at the lateral border of the first rib, extending 3 to 4 cm
have an infection rate comparable to that with radial artery along the undersurface of the clavicle and becoming the bra-
catheters [85]. Although more recent reports suggest that a chiocephalic vein where it joins the ipsilateral IJV at Pirogoffs
catheter properly placed and cared for has a similar rate of in- confluence behind the sternoclavicular articulation (Fig. 2.5).
fection regardless of venipuncture site, CDC guidelines recom- The vein is 1 to 2 cm in diameter, contains a single set of
mend avoidance of the femoral site unless absolutely necessary valves just distal to the EJV junction, and is fixed in position
[77,86]. directly beneath the clavicle by its fibrous attachments. These
Two reports in 1958 highlighted the high incidence of FV attachments prevent collapse of the vein, even with severe vol-
catheter-associated deep venous thrombosis, but these studies ume depletion. Anterior to the vein throughout its course lie
were primarily autopsy based and prior to modern techno- the subclavius muscle, clavicle, costoclavicular ligament, pec-
logical advances. Catheter-associated thrombosis is a risk of toralis muscles, and epidermis. Posteriorly, the SCV is separated
all CVCs, regardless of the site of insertion, and comparative from the subclavian artery and brachial plexus by the anterior
studies using contrast venography, impedance plethysmogra- scalenus muscle, which is 10 to 15 mm thick in the adult. Poste-
phy, or Doppler ultrasound suggest that FV catheters are no rior to the medial portion of the SCV are the phrenic nerve and
more prone to thrombosis than upper extremity catheters. Pul- internal mammary artery as they pass into the thorax. Supe-
monary emboli have been reported following CVC-associated riorly, the relationships are the skin, platysma, and superficial
upper extremity thrombosis [46] and the relative risk of aponeurosis. Inferiorly, the vein rests on the first rib, Sibsons
femoral catheter-related thrombosis is unknown. Clearly, the fascia, the cupola of the pleura (0.5 cm behind the vein), and
potential thromboembolic complications of FV catheters can- pulmonary apex [88]. The thoracic duct on the left and right
not be discounted [87], but they do not warrant total aban- lymphatic duct cross the anterior scalene muscle to join the
donment of this approach. superior aspect of the SV near its union with the IJV.
In summary, available evidence supports the view that the The clavicle presents a significant barrier for ultrasound vi-
FV may be cannulated safely in critically ill adults. It is partic- sualization of the SCV, which mandates using a different ap-
ularly useful for inexperienced operators because of the high proach [12]. Typically, we identify the axillary/subclavian vein
rate of success and lower incidence of major complications. FV junction by placing the probe inferior to the clavicle in the del-
catheterizations may be performed during airway emergencies topectoral groove. We usually initially produce an axial view
and cardiopulmonary arrest, in patients with coagulopathy, in of the vein by placing the probe in the cranialcaudal direction.
patients who are unable to lie flat, and for access during re- The probe is then rotated 90 degrees to produce a longitudinal
nal replacement therapy. The most common major complica- view of the vein, which is maintained during venipuncture and
tion during FV catheterization is arterial puncture, which can guidewire insertion (Fig. 2.6). Although this method is usu-
be lessened or eliminated by ultrasound guidance. Infection is ally successful it tends to be more time consuming and in our
no more common than with IJV catheters. Catheter-associated experience, not as useful.
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Chapter 2: Central Venous Catheters 27

FIGURE 2.5. Anatomy of the subclavian


vein and adjacent structures.

Technique the manubriosternal junction. For the infraclavicular approach


Although there are many variations, the SCV may be can- (Fig. 2.7), the operator is positioned next to the patients shoul-
nulated using surface landmarks by two basic techniques: der on the side to be cannulated. For reasons cited earlier, the
the infraclavicular [89] or supraclavicular [90,91] approach left SCV should be chosen for pulmonary artery catheteriza-
(Fig. 2.7). The differences in success rate, catheter tip malposi- tion; otherwise, the success rate appears to be equivalent re-
tion, and complications between the two approaches are neg- gardless of the side chosen. Skin puncture is 2 to 3 cm cau-
ligible, although catheter tip malposition and pneumothorax dal to the clavicle at the deltopectoral groove, corresponding
may be less likely with supraclavicular cannulation [92,93]. In to the area where the clavicle turns from the shoulder to the
general, when discussing the success rate and incidence of com- manubrium. Skin puncture should be distant enough from the
plications of SV catheterization, there is no need to specify the clavicle to avoid a downward angle of the needle in clearing
approach used. the inferior surface of the clavicle, which also obviates any
The 18-gauge thin-wall needle is preferable for SCV can- need to bend the needle. The path of the needle is toward the
nulation. The patient is placed in a 15- to 30-degree Trende- suprasternal notch. Using maximum barrier precautions, the
lenburg position, and in our experience, use of a small bedroll skin is prepped with chlorhexidine. After skin infiltration and
between the scapulae tends move the humeral head out of the liberal injection of the clavicular periosteum with 1% lidocaine
plane of needle insertion. The head is turned slightly to the and a time-out, the 18-gauge thin-wall needle is mounted on
contralateral side and the arms are kept to the side. The perti- a 10-mL syringe. Skin puncture is accomplished with the nee-
nent landmarks are the clavicle, the two muscle bellies of the dle bevel up, and the needle is advanced in the plane already
SCM, the suprasternal notch, the deltopectoral groove, and described until the tip abuts the clavicle. The needle is then

A B

FIGURE 2.6. Ultrasound view of the subclavian vein. A: Axial view; B: longitudinal view. See text for details.
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28 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

A B

FIGURE 2.7. A: Patient positioning for subclavian cannulation. B: Cannulation technique for supraclav-
icular approach.

walked down the clavicle until the inferior edge is cleared. puncture is the claviculosternocleidomastoid angle, just above
To avoid pneumothorax, it is imperative the needle stay parallel the clavicle and lateral to the insertion of the clavicular head of
to the floor and not angle down toward the chest. This is accom- the SCM. The needle is advanced toward or just caudal to the
plished by using the operators left thumb to provide downward contralateral nipple just under the clavicle. This corresponds to
displacement in the vertical plane after each attempt, until the a 45-degree angle to the sagittal plane, bisecting a line between
needle advances under the clavicle. the sternoclavicular joint and clavicular insertion of the SCM.
As the needle is advanced further, the inferior surface of the The depth of insertion is from just beneath the SCM clavicular
clavicle should be felt hugging the needle. This ensures that the head at a 10- to 15-degree angle below the coronal plane. The
needle tip is as superior as possible to the pleura. The needle needle should enter the jugulosubclavian venous bulb after 1 to
is advanced toward the suprasternal notch during breath hold- 4 cm, and the operator may then proceed with catheterization.
ing or expiration, and venipuncture occurs when the needle tip
lies beneath the medial end of the clavicle. This may require
insertion of the needle to its hub. Blood return may not oc-
Success and Complication Rates
cur until slow withdrawal of the needle. If venipuncture is not Subclavian vein catheterization is successful in 90% to 95%
accomplished on the initial thrust, the next attempt should be of cases, generally on the first attempt [96]. The presence of
directed slightly more cephalad. If venipuncture does not occur shock does not alter the success rate as significantly as it does
by the third or fourth attempt, another site should be chosen, during IJV catheterization [97]. Unsuccessful catheterizations
as additional attempts are unlikely to be successful and may are a result of venipuncture failure or inability to advance the
result in complications. guidewire or catheter. Catheter tip malposition occurs in 5% to
When blood return is established, the bevel of the needle is 20% of cases and tends to be more frequent with the infraclav-
rotated 90 degrees toward the heart. The needle is anchored icular approach. Malposition occurs most commonly to the
firmly with the left hand while the syringe is detached with ipsilateral IJV and contralateral SCV and is usually correctable
the right. Blood return should not be pulsatile, and air em- without repeat venipuncture.
bolism prophylaxis is necessary at all times. The guidewire is The overall incidence of noninfectious complications varies
then advanced through the needle to 15 cm and the needle depending on the operators experience and the circumstances
withdrawn. To increase the success rate of proper placement under which the catheter is inserted. Large series involving sev-
of the catheter, the J-wire tip should point inferiorly [94]. The eral thousand SCV catheters have reported an incidence of ma-
remainder of the procedure is as previously described. Triple- jor complications of 1% to 3%, with an overall rate of 5%.
lumen catheters should be sutured at 15 to 16 cm on the right In smaller, probably more clinically relevant studies, the ma-
and 17 to 18 cm on the left to avoid intracardiac tip placement jor complication rate has ranged from 1% to 10% [98100].
[31,32,95]. Factors resulting in a higher complication rate are operator in-
For the supraclavicular approach (Fig. 2.7), the important experience, multiple attempts at venipuncture, emergency con-
landmarks are the clavicular insertion of the SCM muscle and ditions, variance from standardized technique, and body mass
the sternoclavicular joint. The operator is positioned at the index. Major noninfectious complications include pneumotho-
head of the patient on the side to be cannulated. The site of skin rax, arterial puncture, and thromboembolism. There are many
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Chapter 2: Central Venous Catheters 29

case reports of isolated major complications involving neck IJV catheterization, its use should be limited to those opera-
structures or the brachial plexus; the reader is referred else- tors skilled in the technique. Inexperienced operators should
where for a complete listing of reported complications [11]. use an alternative site. Experienced operators should continue
Pneumothorax accounts for one fourth to one half of re- to use this route for certain indications (Table 2.1) but should
ported complications, with an incidence of about 1.5%. The scrupulously avoid it in patients who cannot tolerate a pneu-
incidence varies inversely with the operators experience and mothorax (severe lung disease, one lung), or in patients with
the number of breaks in technique. There is no magic figure severe coagulopathy, especially platelets <50,000. Ultrasound
whereby an operator matures from inexperienced to experi- guidance may be helpful, but requires a higher skill level and a
enced. Fifty catheterizations are cited frequently as a cutoff different approach to catheterization.
number [101], but it is reasonable to expect an operator to
be satisfactorily experienced after having performed fewer. For
the experienced operator, a pneumothorax incidence of less INFECTIOUS COMPLICATIONS
than 1% is expected. Most pneumothoraces are a result of
lung puncture at the time of the procedure, but late-appearing Tremendous advances in the understanding of the pathophys-
pneumothoraces have been reported. iology, causes, and prevention of CRI have occurred in re-
Most pneumothoraces will require thoracostomy tube cent years and have led to corresponding dramatic improve-
drainage with a small chest tube and a Heimlich valve but some ments in catheter technology, insertion, and management.
can be managed conservatively with 100% oxygen and serial Table 2.2 summarizes current recommendations or interven-
radiographs or needle aspiration only [1]. Rarely, a pneumoth- tions that have been shown to reduce the risk of CRI. This
orax is complicated by tension, blood, infusion of intravenous section reviews these recommendations, focusing on the epi-
fluid (immediately or days to weeks after catheter placement), demiology, pathogenesis, diagnosis, management, and preven-
chyle, or massive subcutaneous emphysema. Bilateral pneu- tion of central CRI.
mothoraces can occur from unilateral attempts at venipunc-
ture. Pneumothorax can result in death, especially when it goes
unrecognized [102]. Definitions and Epidemiology
Subclavian artery puncture occurs in 0.5% to 1.0% of cases,
constituting one fourth to one third of all complications. Ar- Consensus regarding the definition and diagnosis of CRI is a
terial puncture is usually managed easily by applying pressure necessary initial step in discussing catheter-related infectious
above and below the clavicle. Bleeding can be catastrophic in complications. The semiquantitative culture method described
patients with coagulopathy, especially thrombocytopenia. As by Maki et al. [103] for culturing catheter segments is the most
with other routes, arterial puncture may result in arteriovenous accepted technique for diagnosing CRI. Which catheter seg-
fistula or pseudoaneurysm. ment to culture (the tip or intradermal segment) is still con-
Clinical evidence of central venous thrombosis, including troversial; out of convenience, most centers routinely culture
SVC syndrome, development of collaterals around the shoul- the catheter tip. If semiquantitative methods are used, catheter
der girdle, and pulmonary embolism, occurs in 0% to 3% of contamination (probably occurring at time of withdrawal) is
SCV catheterizations, but routine phlebography performed at defined as less than 15 colony-forming units (CFUs) per culture
catheter removal reveals a much higher incidence of thrombotic plate. CRI is a spectrum: growth of greater than or equal to 15
phenomena. The importance of the discrepancy between clin- CFUs is identified as significant colonization (all other cultures
ical symptoms and radiologic findings is unknown, but upper negative and no clinical symptoms); local or exit-site infec-
extremity thrombosis, even if asymptomatic, is not a totally tion (skin site with erythema, cellulitis, or purulence); catheter-
benign condition [46]. Duration of catheterization, catheter related bacteremia (systemic blood cultures positive for iden-
material, and patient condition probably impact the frequency tical organism on catheter segment and no other source);
of thrombosis, but to an uncertain degree. and catheter-related sepsis or septic shock. Alternative meth-
In summary, the SCV is an extremely reliable and useful ods to diagnose CRI include differential time to positivity
route for CVC, but because of the relatively high rate of pneu- [104] and direct Gram [105] or acridine-orange staining [106]
mothorax and the increased success rate of ultrasound-guided of catheters. Using the differential time to positivity, blood

TA B L E 2 . 2
STEPS TO MINIMIZE CENTRAL VENOUS CATHETERIZATION (CVC)-RELATED INFECTION

1. Institution-supported standardized education, with knowledge assessment, of all physicians involved in CVC insertion and care
2. Site preparation with approved chlorhexidine-based preparation
3. Maximal barrier precautions during catheter insertion
4. Use of mobile procedure carts, safety checklist, empowerment of staff
5. Strict protocols for catheter maintenance (including bandage and tubing changes), preferably by dedicated IV catheter team
6. Appropriate site selection, avoiding heavily colonized or anatomically abnormal areas; use of SCV for anticipated CVC of >4 d
7. For anticipated duration of catheterization exceeding 96 hr, use of silver-impregnated cuff, sustained release chlorhexidine
gluconate patch, and/or antibiotic/antiseptic-impregnated catheters
8. Prompt removal of any catheter which is no longer required
9. Remove pulmonary artery catheters and introducers after 5 d
10. Replace any catheter not placed with sterile precautions within 48 hr (i.e., catheter placed in emergency)
11. Use multilumen catheters only when indicated; remove when no longer needed
12. Avoid routine guidewire exchanges
13. Use surgically implanted catheters or PICCs for long term (i.e., >3 wk) or permanent CVC

CVC, central venous catheterization; PICC, peripherally inserted central catheter; SCV, subclavian vein.
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30 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 2 . 3
INFECTION RATES FOR VARIOUS INTRAVASCULAR CATHETERS

IVD-related BSIs
Device per 1,000 days (95% CI)

Peripheral IV catheters 0.6 (0.20.9)


Midline catheters 0.2 (0.00.5)
Arterial catheters 1.4 (0.82.0)
PICCs 0.8 (0.41.2)
Nontunneled CVCs
Nonmedicated 2.9 (2.63.2)
Medicated; Chlorhexadinesilver sulfadiazine 1.3 (1.01.7)
Medicated; minocyclinerifampin 1.2 (0.32.1)
Tunneled CVCs 2.1 (1.03.2)
Pulmonary artery catheters 3.3 (1.94.6)
Nontunneled hemodialysis catheters 6.1 (4.97.4)

Adapted from Maki DG, Kluger DM, Crnich CJ: The risk of bloodstream infection in adults with different
intravascular devices: a systematic review of 200 published prospective studies. Mayo Clin Proc
81:11591171, 2006.
BSI, bloodstream infection; CI, confidence interval; CVC, central venous catheter; IVD, intravascular
device; PICC, peripherally inserted central venous catheter.

cultures are drawn from the catheter and a peripheral vein. If shown that catheters are most commonly infected by bacteria
the time to positive culture is greater than 120 minutes longer colonizing the skin site, followed by invasion of the intrader-
for the peripheral cultures, a diagnosis of CRI is made. This mal catheter tract. Once the external surface of the intrader-
method has good sensitivity, specificity, and the advantage of mal catheter is infected, bacteria can quickly traverse the en-
faster diagnosis. tire length and infect the catheter tip, sometimes encasing the
The morbidity and economic costs associated with CRI are catheter in a slime layer known as a biofilm (coagulase-negative
truly impressive. Estimates vary because the overall incidence staph). From the catheter tip, bacteria may shed into the blood-
of CRI is impacted by so many independent variables, includ- stream, potentially creating metastatic foci of infection [113].
ing type of ICU, catheter type and composition, duration of The pathophysiology of most catheter infections explains why
catheterization, and site of insertion. Furthermore, critical care guidewire exchanges are not effective in preventing or treating
practice is extremely dynamic, and the frequency and type of in- CRI: the colonized tract and, in many cases, biofilm, remain
travascular catheters used changes over time, rendering much intact and quickly reinfect the new catheter [114].
of the data, somewhat out of date. Intravascular devices are The catheter hub(s) also becomes colonized but contributes
now the single most important cause of health-care associated to catheter-related infectious complications less frequently than
bloodstream infection in the United States and Europe, with an the insertion site [115,116]. Hub contamination may be rela-
estimated incidence of 250,000 to 500,000 cases annually in tively more important as a source of infection for certain types
the United States alone [107]. More than 5 million CVCs are in- of catheters (hemodialysis) and the longer the catheter remains
serted annually in the United States, accounting for 15 million in place [117]. Hematogenous seeding of catheters from bac-
CVC-days. Approximately 3% to 9% of all CVCs will become teremia is an infrequent cause of CRI.
infected during clinical use, and the National Healthcare Safety
Network reports rates of CVC-associated bloodstream infec-
tions varying from 1.2 to 5.5 per 1,000 catheter-days depend- Site Preparation and Catheter Maintenance
ing on the location of the patient [108]. A recently completed
systematic review of the literature reported BSI rates for all in- That the majority of CRIs are caused by skin flora highlights
travascular devices [108] (Table 2.3); noncuffed, nontunneled the importance of site sterility during insertion and catheter
CVCs had an average BSI rate of 2.9 per 1,000 catheter-days. maintenance. Organisms that colonize the insertion site orig-
When BSI does occur, often with a resistant organism such as inate from the patients own skin flora or the hands of op-
methicillin-resistant Staphylococcus aureus (MRSA) and VRE, erators. Thorough hand washing and scrupulous attention to
it increases healthcare costs by as much as $20,000 to 40,000, aseptic technique is mandatory during catheter insertion. A
prolongs ICU and hospital stay by several days, and may in- prospective study proved that a nonsterile cap and mask, sterile
crease attributable mortality [109111]. Importantly, it has gown, and a large drape covering the patients head and body
been estimated that as many as 50% of CRIs are preventable (maximal (triple) sterile barriers, compared to sterile gloves
[112], which should serve as a powerful impetus and render it and small drape) reduced the catheter-related bloodstream in-
indefensible for critical care physicians not to implement ev- fection rate sixfold and were highly cost-effective [118]. If a
erything possible to minimize CRI. break in sterile technique occurs during insertion, termination
of the procedure and replacement of contaminated equipment
is mandatory. Use of a mobile catheter cart that can be wheeled
Pathophysiology of Catheter Infection to the patient bedside facilitates maintenance of the sterile
environment.
Assuming that they are not contaminated during insertion, Chlorhexidine is a superior disinfectant and should be used
catheters can become infected from four potential sources: the instead of iodine-based solutions [119,120]. Proper application
skin insertion site, the catheter hub(s), hematogenous seeding, includes liberally scrubbing the site using expanding concentric
and infusate contamination. Animal and human studies have circles. Excessive hair should be clipped with scissors prior to
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 2: Central Venous Catheters 31

application of the antiseptic, as shaving can cause minor skin placed single-lumen catheters for many indications for central
lacerations and disruption of the epidermal barrier to infection. venous access. Because catheter hubs are a potential source
Care of the catheter after insertion is extremely important of infection and triple-lumen catheters can require three times
in minimizing infection, and all medical personnel should fol- the number of tubing changes, it was widely believed that they
low standardized protocols [121]. The number of piggyback would have a higher infection rate. Studies have presented con-
infusions and medical personnel handling tubing changes and flicting results, but overall the data support the view that triple-
manipulation of the catheter site should be minimized. Re- lumen catheters have a modestly higher rate of infection [134
placement of administration sets every 72 to 96 hours is safe 136]. If used efficiently, however, they provide greater intravas-
and cost-efficient [122], unless there are specific recommenda- cular access per device and can decrease the total number of
tions for the infusate (e.g., propofol). Transparent polyurethane catheter days and exposure to central venipuncture. A slight
dressings have become more popular than gauze and tape, but increase in infection rate per catheter is therefore justifiable
have not been found to be superior. It is recommended that from an overall riskbenefit analysis, if multilumen catheters
the transparent dressing be changed every 7 days or sooner are used only when multiple infusion ports are truly indicated.
if damp or soiled. Addition of a silver-impregnated cuff or Finally, it was hoped that routine subcutaneous tunneling
chlorhexidine sponge has been shown to reduce the rate of of short-term CVCs, similar to long-term catheters, might be
CRI and is cost-effective [123,124]. Application of iodophor an effective way to minimize CRI. This approach is rational
or polymicrobial ointments to the skin site at the time of inser- since the long subcutaneous tract acts to stabilize the catheter
tion or during dressing changes does not convincingly reduce and perhaps act as a barrier to bacterial invasion, and great
the overall incidence of catheter infection, and certain polymi- technical skill is not required. A meta-analysis did not support
crobial ointments may increase the proportion of Candida the routine practice of tunneling all percutaneously inserted
infections [125]. CVCs [137], and it is not a common practice. However, further
studies of the tunneling of short-term IJV and FV catheters are
warranted, especially hemodialysis catheters, since these sites
Frequency of Catheter-Related Infection have a higher infection rate and past studies have generally
favored this approach [108,138].
Observing the above-mentioned recommendations for catheter
insertion and maintenance will minimize catheter-associated
infection. Colonization of the insertion site can begin within
24 hours and increases with duration of catheterization; Duration of Catheterization
10% to 40% of catheters may eventually become colonized
The length of catheterization should be based solely on the need
[126]. Catheter-associated bacteremia occurs in 3% to 8% of
for continued catheterization of the patient. No catheter should
catheters [101,127129], although some studies incorporat-
be left in longer than absolutely necessary. Most data suggest
ing newer catheter technologies and procedures have demon-
that the daily risk of infection remains relatively constant and
strated rates of catheter-associated bacteremia of 2% or less
routine replacement of CVCs without a clinical indication does
[130132]. Overall, catheter-infection rates are best expressed
not reduce the rate of CRI [137,139]. Multiple clinical and
as number of episodes per 1,000 days, and although each ICU
experimental studies have also demonstrated that guidewire
should strive for perfection (it is possible to attain and maintain
exchanges neither decrease nor increase infectious risk [140].
the holy grail of zero CRIs over an extended period of time
The above-mentioned recommendations do not necessar-
[1]), each ICU should definitely reach or exceed an appropri-
ily apply to other special-use catheters, which can be ex-
ate benchmark. The NHSN publishes average rates of CRIs for
posed to different clinical situations and risk. Pulmonary artery
different types of ICUs [109]. Table 2.3 provides national ref-
catheters (PACs) and the introducer should be removed after
erences from published literature that has the added advantage
96 to 120 hours because of the increased risk of infection after
of unique data for each specific catheter type [108].
this time [141]. These catheters are at greater risk for infection
because patients are sicker, the introducer used for insertion is
shorter, and catheter manipulations are frequent.
Type of Catheter Catheters inserted for acute temporary hemodialysis histor-
ically have had a higher rate of infection than other percuta-
The data presented earlier are derived from large studies and
neously placed catheters. Factors contributing to the increased
are not necessarily applicable to any given catheter in any spe-
rate have not been completely elucidated, but logically patient
cific ICU because of variations in definitions, types of catheters,
factors probably influence the incidence of infection more than
site of insertion, duration of catheterization, types of fluid in-
the type of catheter or site of insertion [84]. For acutely ill,
fused, and policies regarding routine guidewire changes, all of
hospitalized patients, temporary dialysis catheters should be
which have been implicated at some point as important fac-
managed similarly to other multilumen catheters, recognizing
tors in the incidence of CRI. The duration of catheterization
that the underlying propensity for infection is distinctly higher
in combination with the type of catheter are major factors; the
[108]. As mentioned earlier, perhaps this is the area that tun-
site of insertion is less important. Guidewire changes have an
neling of catheters should be more thoroughly investigated.
important role in evaluation of the febrile catheterized patient,
For ambulatory outpatients, long-term experience with double-
but routine guidewire changes do not prevent infection. Under
lumen, Dacron-cuffed, silicone CVCs inserted in the IJV has
ideal conditions, all of these factors are less important. Long-
been positive [142].
term TPN catheters can be maintained for months with low
rates of infection, and there is no cutoff time at which coloniza-
tion and clinical infection accelerate. Today, when the need for
long-term catheterization is anticipated, surgically implanted Site of Insertion
catheters should be used. These catheters have low infection
rates and are never changed routinely [133]. PICCs are also an The condition of the site is more important than the location.
acceptable option for patients requiring long-term CVC. Whenever possible, sites involved by infection, burns, or other
Catheters inserted percutaneously in the critical care unit, dermatologic processes, or in close proximity to a heavily col-
however, are not subject to ideal conditions and have a finite onized area (e.g., tracheostomy) should not be used as primary
lifespan. For practical purposes, multilumen catheters have re- access. Data tends to support that PICC and SCV catheters
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32 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

are associated with the lowest rate of CRI, and IJV and FV 0 per 1,000 catheter days. These simple interventions were:
catheters the highest [101]. education of physicians and nurses of evidence-based infection
control practices, creation of a central catheter insertion cart
which contained every item needed for insertion of a catheter,
Guidewire Exchanges daily questioning of whether catheters could be removed, a bed-
side checklist for insertion of catheters, and empowering nurses
Guidewire exchanges have always been theoretically flawed as to stop procedures where the infection control guidelines were
a form of infection control, because although a new catheter is not being followed [146]. Similar interventions in Pennsylvania
placed, the site, specifically the intradermal tract, remains the reduced their CRI rate from 4.31 to 1.36 per 1,000 catheter
same. Studies have shown that when the tract and old catheter days [147]. A statewide initiative in Michigan, the Keystone
are colonized, the new catheter invariably also becomes in- Project, implemented these strategies on a large scale over the
fected. Alternatively, if the initial catheter is not colonized, entire state with equally impressive results [1]. Despite the fact
there is no reason the new catheter will be more resistant to that these and other simple systems interventions and imple-
subsequent infection than the original one. In neither situation mentation require very little capital outlay, many ICUs have
will a guidewire change prevent infection. However, guidewire yet to adopt them [148,149].
changes continue to have a valuable role for replacing defec-
tive catheters, exchanging one type of catheter for another, and
in the evaluation of a febrile patient with an existing central
catheter. In the latter situation, the physician can assess the MANAGEMENT OF THE FEBRILE
sterility of the catheter tract without subjecting the patient to PATIENT
a new venipuncture. However one decides to use guidewire
exchanges, they must be performed properly. Using maximal Patients with a CVC frequently develop fever. Removal of the
barriers, the catheter should be withdrawn until an intravascu- catheter in every febrile patient is neither feasible nor clini-
lar segment is exposed, transected sterilely, and the guidewire cally indicated, as the fever is often unrelated to the catheter.
inserted through the distal lumen. The catheter fragment can Management must be individualized (Fig. 2.7) and depends on
then be removed (always culture the tip) and a new catheter type of catheter, duration of catheterization, anticipated need
threaded over the guidewire. To ensure sterility, most operators for continued central venous access, risk of establishing new
should re-prep the site and change gloves before inserting the central venous access, and underlying medical condition and
new catheter or introducer over the guidewire. Insertion of the prognosis. All critical care units must have protocols for man-
guidewire through the distal hub of the existing catheter is not aging the febrile, catheterized patient [150]. Decisions to re-
appropriate. move, change over a guidewire, or leave catheters in place must
be based on a fundamental knowledge of risks and benefits for
catheters inserted at each site.
NEW CATHETER TECHNOLOGIES Catheter sites in the febrile patient should always be ex-
amined. Clinical infection of the site mandates removal of
Improvements in catheter technology continue to play an im- the catheter and institution of antibiotics. Surgically implanted
portant role in minimizing catheter complications. Catheter catheters are not easily removed or replaced and can often be
material is an important factor in promoting thrombogenesis left in place while the infection is cleared with antibiotics, unless
and adherence of organisms. Most catheters used for CVC are tunnel infection is present. Percutaneously inserted CVCs are
composed of flexible silicone (for surgical implantation) and relatively easily removed, and the risks of leaving a catheter in
polyurethane (for percutaneous insertion), because research place through an infected site outweigh the risk of replacement
has shown these materials are less thrombogenic. Knowledge at a new site, except in very unusual circumstances.
of the pathogenesis of most CRI has stimulated improvements In patients with severe sepsis or septic shock, CVCs should
designed to interrupt bacterial colonization of the skin site, be considered a possible source. If all catheter sites appear
catheter, and intradermal tract, and migration to the catheter normal and a noncatheter source of infection is implicated,
tip. Antibiotic and antiseptic impregnated catheters represent a appropriate antibiotics are initiated and the catheters left in
major advance in catheter management. Catheters differ from place. The usual guidelines for subsequent catheter manage-
one another by the type of antibiotic or antiseptic with which ment should be followed, and this rarely results in treatment
they are impregnated. Clinical results with these commercially failure. In contrast, if a noncatheter source cannot be identi-
available catheters have been variable [143,144], likely due to fied, then central catheters in place more than 3 days should be
varying practices and the baseline infection rate. Good ran- managed individually, with attention to duration of catheter-
domized controlled trials comparing the various types of anti- ization (Table 2.3). Only for patients with excessive risks for
septic catheters with each other are lacking, but we believe that new catheter placement (i.e., severe coagulopathy), guidewire
current evidence supports using one of the above catheters if exchange of the catheter is justifiable after obtaining blood
the baseline CRI rate remains high after instituting infection cultures through the catheter and a peripheral site and semi-
control practices [101,132,133]. The preponderance of data quantitative culture of a catheter segment. If within the next 24
indicates that in real-life practice, these catheters decrease the hours an alternative source for sepsis is found, or if the catheter
rate of CRI and improve patient safety, likely at a neutral or fa- segment culture is negative and the patient improves and stabi-
vorable cost [129,145]. The emergence of resistant organisms lizes, the guidewire catheter can be left in place and the risk of
and allergic reactions has not yet been a problem, but ongoing catheter insertion avoided. Alternatively, if the catheter culture
surveillance is needed. becomes positive, especially if the same organism is identified
on peripheral blood cultures, the cutaneous tract is also infected
and the guidewire catheter should be removed and alternative
SYSTEMS-BASED MEASURES access achieved.
The most common situation is the stable febrile patient
Not surprisingly, evidence is pointing to systems-based fac- with a CVC in place (Table 2.4). As mentioned earlier, if a
tors as being more important in reducing the incidence of CRI noncatheter source for fever is identified, appropriate antibi-
than any new technology. At Johns Hopkins, the addition of otics are given and the catheter is left in place, assuming it is
five systems-based changes reduced the CRI rate from 11.3 to still needed and the site is clinically uninvolved. In the patient
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Chapter 2: Central Venous Catheters 33

TA B L E 2 . 4
APPROACH TO THE FEBRILE PATIENT WITH A CENTRAL VENOUS CATHETER

1. Catheter no longer neededremove and culture tip


2. Patient with severe sepsis or septic shock (catheter >72 hr)promptly remove catheter and culture tip
3. Patient with severe sepsis or septic shock (catheter <72 h)initiate antibiotics, remove catheter if no improvement in 1224 h
4. Stable patient (catheter >72 h)guidewire exchange with tip culture if culture with 15 CFUremove catheter

with no obvious source of fever [1], indications for the CVCs cultures without subjecting the patient to repeat venipuncture.
should be reviewed and the catheter withdrawn if it is no longer If within the next 24 hours an alternative source for fever is
required. Otherwise, the physician must decide between ob- identified, and/or the initial catheter segment culture is nega-
servation, potential premature withdrawal, and a guidewire tive, then the guidewire catheter can be left in place.
change of the catheter. If the catheter is less than 72 hours When catheter-related bacteremia does develop, antibiotic
old, observation is reasonable, as it is very unlikely that the therapy is necessary for a period of 7 to 14 days. Even in pa-
catheter is already infected unless breaks in sterile technique oc- tients treated for 14 days, metastatic infection can develop.
curred during insertion. For catheters that are at least 72 hours Catheter-related fever, infection, and septicemia is a compli-
old, guidewire exchanges are rational but, in our opinion, not cated disease, and the expertise of an infectious disease consul-
mandatory. An appropriately performed guidewire change al- tant may be required to assist with the decision on how long
lows comparison of catheter segment cultures to other clinical to continue antibiotic therapy.

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P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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36 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

CHAPTER 3 ARTERIAL LINE PLACEMENT


AND CARE
JASON LEE-LLACER AND MICHAEL G. SENEFF

Arterial catheterization remains an extremely important skill nostic. Waveform inspection can rapidly diagnose electrocar-
for critical care physicians. The most common indications for diogram lead disconnect, indicate the presence of aortic valve
inserting an arterial catheter remain the need for close blood disease, help determine the effect of dysrhythmias on perfusion,
pressure monitoring and frequent blood gas sampling in unsta- and reveal the impact of the respiratory cycle on blood pres-
ble and ventilated patients. Newer technologies that necessitate sure (pulsus paradoxus). In addition, in mechanically ventilated
arterial access continue to mature. For example, arterial pulse patients, responsiveness to fluid boluses may be predicted by
contour analysis can now be used to predict fluid responsive- calculating the systolic pressure variation (SPV) or pulse pres-
ness and compute cardiac output more reliably and less inva- sure variation (PPV) from the arterial waveform, and stroke
sively in appropriately selected patients [1]. Although it is likely volume variation (SVV) from the pulse contour analysis. In pa-
that advancements in current noninvasive technology, such as tients on volume-controlled mechanical ventilation, all of these
transcutaneous PCO2 monitoring and pulse oximetry, will de- techniques have been shown to predict, with a high degree of
crease the need for arterial catheter placement, intensivists will accuracy, patients likely to respond (with an increase in stroke
always need to be knowledgeable in the setup and interpreta- volume) to fluid volume challenge [1].
tion of arterial catheter systems. In this chapter, we review the Recent advances allow continuous CO monitoring using
principles of hemodynamic monitoring and discuss the indica- arterial pulse contour analysis. This method relies on the as-
tions, routes, and management of arterial cannulation. sumption that the contour of the arterial pressure waveform is
proportional to the stroke volume [6]. This, however, does not
take into consideration the differing impedances among the
arteries of individuals and different disease states and there-
INDICATIONS FOR ARTERIAL fore requires calibration with another method of determining
CANNULATION cardiac output [7]. This is usually done with lithium dilution
or transpulmonary thermodilution methods. A different pulse
Arterial catheters should be inserted only when they are specif- contour analysis device has been introduced which does not re-
ically required and removed immediately when no longer quire an additional method of determining CO for calibration,
needed. Too often they are left in place for convenience to al- but instead estimates impedance based upon a proprietary for-
low easy access to blood sampling, which leads to increased mula that uses waveform and patient demographic data [7].
laboratory testing and excessive diagnostic blood loss [2,3]. This method has significant limitations (i.e., atrial fibrillation)
Protocols incorporating guidelines for arterial catheterization and there is concern that the device may not be accurate in
and alternative noninvasive monitoring, such as pulse oxime- clinical situations with dynamic changes in vascular tone (i.e.,
try and end tidal CO2 , have realized significant improvements sepsis) [8]. Further data and comparison among the methods
in resource utilization and cost savings, without impacting the in authentic and diverse clinical situations are required before
quality of care [4]. definitive recommendations can be made.
The indications for arterial cannulation can be grouped into Management of complicated patients in critical care units
four broad categories (Table 3.1): (1) hemodynamic monitor- typically requires multiple laboratory and arterial blood gas de-
ing (blood pressure and/or cardiac output/pulse contour anal- terminations. In these situations, arterial cannulation permits
ysis); (2) frequent arterial blood gas sampling; (3) diagnostic routine laboratory tests without multiple needle sticks and ves-
or therapeutic/interventional radiology procedures, including sel trauma. In our opinion, an arterial catheter for blood gas
intra-aortic balloon pump (IABP) use, arterial administration determination should be placed when a patient requires two or
of drugs, vascular stenting and embolization, and (4) continu- more measurements daily.
ous cardiac output monitoring.
Noninvasive, indirect blood pressure measurements deter-
mined by auscultation of Korotkoff sounds distal to an occlud-
ing cuff (RivaRocci method) are generally accurate, although
EQUIPMENT, MONITORING,
systolic readings are consistently lower compared to a si- TECHNIQUES, AND
multaneous direct measurement. In hemodynamically unstable SOURCES OF ERROR
patients, however, indirect techniques may significantly under-
estimate blood pressure. Automated noninvasive blood pres- The equipment necessary to display and measure an arterial
sure measurement devices can also be inaccurate, particularly waveform has not changed and includes (a) an appropriate in-
in rapidly changing situations, at the extremes of blood pres- travascular catheter; (b) fluid-filled noncompliant tubing with
sure, and in patients with dysrhythmias [5]. For these reasons, stopcocks; (c) transducer; (d) a constant flush device; and (e)
direct blood pressure monitoring is usually required for unsta- electronic monitoring equipment. Using this equipment, in-
ble patients. Rapid beat-to-beat changes can easily be mon- travascular pressure changes are transmitted through the hy-
itored and appropriate therapeutic modalities initiated, and draulic (fluid-filled) elements to the transducer, which converts
variations in individual pressure waveforms may prove diag- mechanical displacement into a proportional electrical signal.
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Chapter 3: Arterial Line Placement and Care 37

TA B L E 3 . 1 The damping coefficient is a measure of how quickly an


oscillating system comes to rest. A system with a high damp-
INDICATIONS FOR ARTERIAL CANNULATION ing coefficient absorbs mechanical energy well (i.e., compliant
tubing), causing a diminution in the transmitted waveform.
Hemodynamic monitoring Conversely, a system with a low damping coefficient results in
Acutely hypertensive or hypotensive patients underdamping and systolic overshoot. Damping coefficient and
Use of vasoactive drugs resonant frequency together determine the dynamic response
Multiple blood sampling of a recording system. If the resonant frequency of a system
Ventilated patients is less than 7.5 Hz, the pressure waveform will be distorted
Limited venous access no matter what the damping coefficient. On the other hand,
a resonant frequency of 24 Hz allows a range in the damping
Diagnostic or interventional radiology procedures
coefficient of 0.15 to 1.1 without resultant distortion of the
Intra-arterial drugs
pressure waveform [9].
Vascular stenting
Although there are other techniques [12], the easiest method
Intra-aortic balloon pump use
to test the damping coefficient and resonant frequency of a
Arterial embolization
monitoring system is the fast-flush test (also known as the
Continuous cardiac output monitoring square wave test). This is performed at the bedside by briefly
opening and closing the continuous flush device, which pro-
duces a square wave displacement on the monitor followed
by a return to baseline, usually after a few smaller oscillations
The signal is amplified, processed, and displayed as a waveform (Fig. 3.1). Values for the damping coefficient and resonant fre-
by the monitor. Undistorted presentation of the arterial wave- quency can be computed by printing the wave on graph paper
form is dependent on the performance of each component, and [9], but visual inspection is usually adequate to ensure a proper
an understanding of potential problems that can interfere with frequency response. An optimum fast-flush test results in one
overall fidelity of the system. undershoot followed by small overshoot, then settles to the
The major problems inherent to pressure monitoring with patients waveform.
a catheter system are inadequate dynamic response, improper For peripheral pulse pressure monitoring, an adequate fast-
zeroing and zero drift, and improper transducer/monitor cali- flush test usually corresponds to a resonant frequency of 10
bration. Most physicians are aware of zeroing techniques but to 20 Hz coupled with a damping coefficient of 0.5 to 0.7. To
do not appreciate the importance of dynamic response in ensur- ensure the continuing fidelity of a monitoring system, dynamic
ing system fidelity. Catheter-tubing-transducer systems used for response validation by fast-flush test should be performed fre-
pressure monitoring can best be characterized as underdamped quently: at least every 8 hours, with every significant change in
second-order dynamic systems with mechanical parameters of patient hemodynamic status, after each opening of the system
elasticity, mass, and friction [9]. Overall, the dynamic response (zeroing, blood sampling, tubing change), and whenever the
of such a system is determined by its resonant frequency and waveform appears damped [9].
damping coefficient (zeta). The resonant or natural frequency With consideration of the above concepts, components of
of a system is the frequency at which it oscillates when stimu- the monitoring system are designed to optimize the frequency
lated. When the frequency content of an input signal (i.e., pres- response of the entire system. The 18- and 20-gauge catheters
sure waveform) approaches the resonant frequency of a system, used to gain vascular access are not a major source of distortion
progressive amplification of the output signal occursa phe- but can become kinked or occluded by thrombus, resulting in
nomenon known as ringing [10]. To ensure a flat frequency re- overdamping of the system. Standard, noncompliant tubing is
sponse (accurate recording across a spectrum of frequencies), provided with most disposable transducer kits and should be
the resonant frequency of a monitoring system should be at as short as possible to minimize signal amplification [10]. Air
least five times higher than the highest frequency in the input bubbles in the tubing and connecting stopcocks are a notori-
signal [9]. Physiologic peripheral arterial waveforms have a ous source of overdamping of the tracing and can be cleared
fundamental frequency of 3 to 5 Hz and therefore the resonant by flushing through a stopcock. Currently available disposable
frequency of a system used to monitor arterial pressure should transducers incorporate microchip technology, are very reli-
ideally be greater than 20 Hz to avoid ringing and systolic able, and have relatively high resonant frequencies [13]. The
overshoot. transducer is attached to the electronic monitoring equipment
The system component most likely to cause amplification by a cable. Modern monitors have internal calibration, filter
of a pressure waveform is the hydraulic element. A good hy- artifacts, and print the display on request. The digital readout
draulic system will have a resonant frequency between 10 and display is usually an average of values over time and therefore
20 Hz, which may overlap with arterial pressure frequencies. does not accurately represent beat-to-beat variability. Moni-
Thus amplification can occur, which may require damping to tors provide the capability to freeze a display with on-screen
accurately reproduce the waveform [11]. calibration to measure beat-to-beat differences in amplitude

FIGURE 3.1. Fast-flush test. A: Overdamped


system. B: Underdamped system. C: Optimal
A B C damping.
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38 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

precisely. This allows measurement of the effect of ectopic beats superficial temporal arteries. Peripheral sites are cannulated
on blood pressure, PPV, SPV, or assessment of the severity of percutaneously with a 2-inch, 20-gauge, nontapered Teflon
pulsus paradoxus. catheter-overneedle and larger arteries using the Seldinger tech-
When presented with pressure data or readings believed to nique with a prepackaged kit, typically containing a 6-inch,
be inaccurate, or which are significantly different from indirect 18-gauge Teflon catheter, appropriate introducer needles, and
readings, a few quick checks can ensure system accuracy. Im- guidewire.
proper zeroing of the system, because of either change in patient Arterial catheterization is performed by physicians from
position or zero drift, is the single most important source of er- many different specialties and usually the procedure to be per-
ror. Zeroing can be checked by opening the transducer stopcock formed dictates the site chosen. For example, insertion of an
to air and aligning with the midaxillary line, confirming that the IABP is almost always performed through the femoral artery
monitor displays zero. Zeroing should be repeated with patient regardless of the specialty of the physician performing the pro-
position changes, (a transducer that is below the zero reference cedure. Critical care physicians need to be facile with arterial
line will result in falsely high readings and vice versa), when sig- cannulation at all sites, but the radial and femoral arteries are
nificant changes in blood pressure occur, and routinely every 6 used successfully for more than 90% of all arterial catheteri-
to 8 hours because of zero drift. Disposable pressure transduc- zations performed in the ICU. Although each site has unique
ers incorporate semiconductor technology and are very small, complications, available data do not indicate a preference for
yet rugged and reliable, and due to standardization, calibration any one site [1517]. Radial artery cannulation is usually at-
of the system is not necessary [13]. Transducers are faulty on tempted initially unless the patient is in shock, on high dose va-
occasion, however, and calibration may be checked by attach- sopressors, and/or pulses are not palpable. If this fails, femoral
ing a mercury manometer to the stopcock and applying 100, artery cannulation should be performed. If catheterization at
150, and/or 200 mm Hg pressure. A variation of 5 mm Hg these two sites proves unsuccessful or not appropriate, then
is acceptable. If calibration is questioned and the variation is the dorsalis pedis, brachial, and axillary artery are the recom-
out of range, or a manometer is not available for testing, the mended alternative sites. Which of these is chosen depends on
transducer should be replaced. the exact clinical situation and the experience and expertise of
If zero referencing and calibration are correct, a fast-flush the operator.
test will assess the systems dynamic response. Overdamped
tracings are usually caused by problems that are correctable,
such as air bubbles, kinks, clot formation, overly compliant
tubing, loose connections, a deflated pressure bag, or anatom- Use of Portable Ultrasound
ical factors affecting the catheter. An underdamped tracing re-
Bedside ultrasound has not had as great an impact on arterial
sults in systolic overshoot and can be secondary to excessive
as it has on venous catheterization because vessel puncture is
tubing length or patient factors such as increased inotropic or
based on a palpable landmark that guides needle placement,
chronotropic state. Many monitors can be adjusted to filter
and the complication rate during insertion is much lower. How-
out frequencies above a certain limit, which can eliminate fre-
ever, we have found ultrasound guidance to be very useful and
quencies in the input signal causing ringing. However, this may
efficient in assisting with brachial and femoral artery catheteri-
also cause inaccurate readings if important frequencies are ex-
zations, and have even used it successfully for selected difficult
cluded.
radial artery procedures. In our experience, ultrasound has the
same impact with arterial as it does with venous catheteriza-
tions; higher success rate with less procedure time, number of
TECHNIQUE OF ARTERIAL attempts, and complications. Operator technique of ultrasound
CANNULATION for arterial is the same as for venous catheterization and the
reader is referred to Chapter 2 for a description of ultrasound
equipment and technique. Ultrasound images for each of the
Site Selection major arterial routes are shown in Figure 3.2.
Several factors are important in selecting the site for arterial
cannulation. The ideal artery has extensive collateral circula-
tion that will maintain the viability of distal tissues if throm- Radial Artery Cannulation
bosis occurs. The site should be comfortable for the patient,
accessible for nursing care and insertion, and close to the mon- A thorough understanding of normal arterial anatomy and
itoring equipment. Sites involved by infection or disruption in common anatomical variants greatly facilitates insertion of
the epidermal barrier should be avoided. Certain procedures, catheters and management of unexpected findings at all sites.
such as coronary artery bypass grafting, may dictate preference The radial artery is one of two final branches of the brachial
for one site over another. Larger arteries and catheters provide artery. It courses over the flexor digitorum sublimis, flexor pol-
more accurate (central aortic) pressure measurements. Physi- licis longus, and pronator quadratus muscles and lies just lat-
cians should also be cognizant of differences in pulse contour eral to the flexor carpi radialis in the forearm. As the artery
recorded at different sites. As the pressure pulse wave travels enters the floor of the palm, it ends in the deep volar arterial
outward from the aorta, it encounters arteries that are smaller arch at the level of the metacarpal bones and communicates
and less elastic, with multiple branch points, causing reflections with the ulnar artery. A second site of collateral flow for the
of the pressure wave. This results in a peripheral pulse contour radial artery occurs via the dorsal arch running in the dorsum
with increased slope and amplitude, causing recorded values of the hand (Fig. 3.3).
to be artificially elevated. As a result, distal extremity artery The ulnar artery runs between the flexor carpi ulnaris and
recordings yield higher systolic values than central aortic or flexor digitorum sublimis in the forearm, with a short course
femoral artery recordings. Diastolic pressures tend to be less over the ulnar nerve. In the hand the artery runs over the trans-
affected, and mean arterial pressures measured at the different verse carpal ligament and becomes the superficial volar arch,
sites are similar [14]. which forms an anastomosis with a small branch of the radial
The most commonly used sites for arterial cannulation in artery. These three anastomoses provide excellent collateral
adults are the radial, femoral, axillary, dorsalis pedis, and flow to the hand [18]. A competent superficial or deep pal-
brachial arteries. Additional sites include the ulnar, axillary and mar arch must be present to ensure adequate collateral flow.
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Chapter 3: Arterial Line Placement and Care 39

A
B

C D

FIGURE 3.2. Portable ultrasound images. A. Radial artery longitudinal view. B. Brachial artery axial
view. C. Femoral artery axial view. D. Axillary artery axial view. See text for details.

At least one of these arches may be absent in up to 20% of catheter that suggests decreased perfusion (color or tempera-
individuals. ture change, paresthesias, loss of capillary refill) should prompt
immediate removal of the catheter and further investigation if
the changes do not reverse.
Modified Allens Test
Hand ischemia is a rare but potential devastating complication
of radial artery catheterization that may require amputation
[19]. Hand ischemia is rare because of the rich collateral cir- Percutaneous Insertion
culation described earlier that insures perfusion even if one of
the main arteries thrombose. Historically, the modified Allens The hand is positioned in 30 to 60 degrees of dorsiflexion with
test [20], described in previous editions of this text, was used the aid of a roll of gauze and armband, avoiding hyperabduc-
prior to radial catheterization to detect patients in whom the tion of the thumb. The volar aspect of the wrist is prepared
collateral circulation may not be intact and presumably at in- (alcoholic chlorhexidine) and draped using sterile technique,
creased risk for hand ischemia. However, as a screening tool and approximately 0.5 mL of lidocaine is infiltrated on both
the Allens test has never had very good predictive value [21] sides of the artery through a 25-gauge or smaller needle. Lido-
and our institution, as well as many others, has abandoned its caine serves to decrease patient discomfort and may decrease
routine use. The best way to prevent hand ischemia is to avoid the likelihood of arterial vasospasm [22]. The catheter over the
radial catheterization in patients at increased risk (i.e., high needle approach (e.g., radial or brachial site) necessitates cap,
dose vasopressor therapy, scleroderma, vasculopathy) and to mask, sterile gloves and a small fenestrated drape; whereas, the
perform clinical evaluation of hand perfusion at each nursing Seldinger technique (i.e., femoral approach) requires maximum
shift change. Any change in the hand distal to a radial artery barrier precautions. A time out confirming correct patient,
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40 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

Catheters with self-contained guidewires to facilitate pas-


sage of the cannula into the artery are available (Fig. 3.4).
Percutaneous puncture is made in the same manner, but when
blood return is noted in the catheter hub the guidewire is passed
through the needle into the artery, serving as a stent for subse-
quent catheter advancement. The guidewire and needle are then
removed and placement confirmed by pulsatile blood return.
The cannula is then secured firmly, attached to transducer tub-
ing, and the site bandaged. Video instruction for the insertion
of a radial arterial line is available at www.nejm.org [24].

Dorsalis Pedis Artery Cannulation


Dorsalis pedis artery catheterization is uncommon in most crit-
ical care units; compared with the radial artery, the anatomy
is less predictable and the success rate is lower [25]. The dor-
salis pedis artery is the main blood supply of the dorsum of the
foot. The artery runs from the level of the ankle to the great
toe. It lies very superficial and just lateral to the tendon of the
extensor hallucis longus. The dorsalis pedis anastomoses with
branches from the posterior tibial (lateral plantar artery) and,
to a lesser extent, peroneal arteries, creating an arterial arch
network analogous to that in the hand.
Use of a catheter with self-contained guidewire is recom-
mended for dorsalis pedis catheterization. The foot is placed in
plantar flexion and prepared in the usual fashion. Vessel entry
is obtained approximately halfway up the dorsum of the foot
where the palpable pulse is strongest; advancement is the same
as with cannulation of the radial artery. Patients usually find
insertion here more painful but less physically limiting. Sys-
tolic pressure readings are usually 5 to 20 mm Hg higher with
dorsalis pedis catheters than radial artery catheters, but mean
pressure values are generally unchanged.

FIGURE 3.3. Anatomy of the radial artery. Note the collateral circula-
tion to the ulnar artery through the deep volar arterial arch and dorsal Brachial Artery Cannulation
arch.
The brachial artery is cannulated in the bicipital groove prox-
imal to the antecubital fossa at a point where there is no
correct site, correct equipment and informed consent is nec- collateral circulation (Fig. 3.2B). In theory, clinical ischemia
essary before the procedure begins. should be a greater risk, but in most series brachial artery
A 20-gauge, nontapered, Teflon 11/2- or 2-inch catheter- catheters have complication rates comparable to other routes
overneedle apparatus is used for puncture. Entry is made at [17,18,26,27]. Even when diminution of distal pulses occurs,
a 30- to 60-degree angle to the skin approximately 3 to 5 cm because of either proximal obstruction or distal embolization,
proximal to the distal wrist crease. Ultrasound image of the clinical ischemia is unlikely [26]. An additional anatomic con-
radial artery at this position is shown in Figure 3.2A. The sideration is that the median nerve lies in close proximity to the
needle and cannula are advanced until blood return is noted brachial artery and may be punctured in 1% to 2% of cases
in the hub, signifying intra-arterial placement of the tip of the [27]. This usually causes only transient paresthesias, but me-
needle. A small amount of further advancement is necessary for dian nerve palsy has been reported. Median nerve palsy is a par-
the cannula to enter the artery as well. With this accomplished, ticular risk in patients with coagulopathy because even minor
needle and cannula are brought flat to the skin and the cannula bleeding into the fascial planes can produce compression of the
advanced to its hub with a firm, steady rotary action. Correct median nerve [28]. Coagulopathy should be considered a rela-
positioning is confirmed by pulsatile blood return on removal tive contraindication to brachial artery cannulation. Given all
of the needle. If the initial attempt is unsuccessful, subsequent these considerations, brachial artery cannulation should only
attempts should be more proximal, rather than closer to the be considered if the radial, femoral, and dorsalis pedis sites are
wrist crease, as the artery is of greater diameter [18], although not available or appropriate.
this may increase the incidence of catheters becoming kinked Cannulation of the brachial artery is best performed using a
or occluded [23]. prepackaged kit designed for larger arteries (see femoral artery
If difficulty is encountered when attempting to pass the cannulation). The brachial artery is punctured by extending the
catheter, carefully replacing the needle and slightly advancing arm at the elbow and locating the pulsation a few centimeters
the whole apparatus may remedy the problem. Alternately, a proximal to the antecubital fossa, just medial to the bicipi-
fixation technique can be attempted (Fig. 3.3). Advancing the tal tendon. Once the catheter is established, the elbow must be
needle and catheter through the far wall of the vessel purposely kept in full extension to avoid kinking or breaking the catheter.
transfixes the artery. The cannula is then pulled back with the Clinical examination of the hand, and Doppler studies if indi-
needle partially retracted within the catheter until vigorous ar- cated, should be repeated daily while the brachial catheter is
terial blood return is noted. The catheter can then be advanced in place. The catheter should be promptly removed if diminu-
into the arterial lumen, using the needle as a reinforcing stent. tion of any pulse occurs or there is evidence of embolism. An
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Chapter 3: Arterial Line Placement and Care 41

C
A

B D

FIGURE 3.4. Cannulation of the radial artery. A: A towel is placed behind the wrist, and the hand is
immobilized with tape. B: The catheter-needle-guidewire apparatus is inserted into the skin at a 30- to
60-degree angle. C: The guidewire is advanced into the artery after pulsatile blood flow is obtained. D: The
catheter is advanced over the guidewire into the artery. [From Irwin RS, Rippe JM: Manual of Intensive
Care Medicine. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2006:17, with permission.]

additional concern is air embolism (see later) since placement and the middle third of a straight line drawn between the pu-
of a 6-inch catheter puts the tip in the axillary artery. bis and the anterior superior iliac spine (Fig. 3.2C). The artery
is cannulated using the Seldinger technique and any one of
several available prepackaged kits. Kits contain the equivalent
Femoral Artery Cannulation of a 19-gauge thin-wall needle, appropriate guidewire, and a
6-inch, 18-gauge Teflon catheter. The patient lies supine with
The femoral artery is usually the next alternative when ra- the leg extended and slightly abducted. Skin puncture should
dial artery cannulation fails or is inappropriate [1517]. The be 3 to 5 cm caudal to the inguinal ligament to minimize
femoral artery is large and often palpable when other sites are the risk of retroperitoneal hematoma or bowel perforation,
not, and the technique of cannulation is easy to learn. The most which can occur when needle puncture of the vessel is cepha-
common reason for failure to cannulate is severe atheroscle- lad to the inguinal ligament. The thin-wall needle is directed,
rosis or prior vascular procedures involving both femoral ar- bevel up, cephalad at a 45-degree angle. When arterial blood
teries, in which case axillary or brachial artery cannulation is return is confirmed, the needle and syringe may need to be
appropriate. Complications unique to this site are rare but in- brought down against the skin to facilitate guidewire passage.
clude retroperitoneal hemorrhage and intra-abdominal viscus The guidewire should advance smoothly, but minor manip-
perforation. These complications occur because of poor tech- ulation and rotation is sometimes required if the wire meets
nique (puncture above the inguinal ligament) or in the presence resistance at the needle tip or after it has advanced into the
of anatomical variations (i.e., large inguinal hernia). Ischemic vessel. Inability to pass the guidewire may be due to an inti-
complications from femoral artery catheters are very rare. mal flap over the needle bevel or atherosclerotic plaques in the
The external iliac artery becomes the common femoral vessel. In the latter instance, cannulation of that femoral artery
artery at the inguinal ligament (Fig. 3.5). The artery courses may prove impossible. When the guidewire will not pass be-
under the inguinal ligament near the junction of the medial yond the needle tip it should be withdrawn and blood return
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42 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

is enclosed in a neurovascular bundle, the axillary sheath, with


the medial, posterior, and lateral cords of the brachial plexus.
Medial to the medial cord is the axillary vein. Not surprisingly,
brachial plexus neuropathies have been reported from axillary
artery cannulation [30]. Coagulopathy is a relative contraindi-
cation, as the axillary sheath can rapidly fill with blood from
an uncontrolled arterial puncture, resulting in a compressive
neuropathy.
The axillary artery is cannulated using the Seldinger tech-
nique and a prepackaged kit. The arm is abducted, externally
rotated, and flexed at the elbow by having the patient place
the hand under his or her head. The artery is palpated at the
lower border of the pectoralis major muscle and fixed against
the shaft of the humerus. After site preparation and local in-
filtration with lidocaine, the thin-wall needle is introduced at
a 30- to 45-degree angle to the vertical plane until return of
arterial blood. The remainder of the catheterization proceeds
as described for femoral artery cannulation.

COMPLICATIONS OF ARTERIAL
CANNULATION
Arterial cannulation is a relatively safe invasive procedure. Al-
though estimates of the total complication rate range from 15%
to 40%, clinically relevant complications occur in 5% or less
(Table 3.2). Risk factors for infectious and noninfectious com-
plications have been identified [31,32] (Table 3.3), but the clin-
ical impact of most of these factors is minimal, given the overall
low incidence of complications.

Thrombosis
FIGURE 3.5. Anatomy of the femoral artery and adjacent structures. Thrombosis is the single most common complication of intra-
The artery is cannulated below the inguinal ligament.
arterial catheters. The incidence of thrombosis varies with the
site, method of detection, size of the cannula, and duration of

reestablished by advancing the needle or repeat vascular punc-


ture. The guidewire is then inserted, the needle withdrawn TA B L E 3 . 2
and the catheter threaded over the guidewire to its hub. The
guidewire is withdrawn, the catheter sutured securely and con- COMPLICATIONS ASSOCIATED WITH ARTERIAL
nected to the transducer tubing. CANNULATION

Site Complication

Axillary Artery Cannulation All sites Pain and swelling


Thrombosis
Axillary artery catheterization in the ICU occurs infrequently, Asymptomatic
but centers experienced with it report a low rate of compli- Symptomatic
cations [15,17,29]. The axillary artery is large and frequently Embolization
palpable when all other sites are not and has a rich collateral Hematoma
circulation. The tip of a 6-inch catheter inserted through an Hemorrhage
axillary approach lies in the subclavian artery, and thus ac- Limb ischemia
curate central pressures are obtained. The central location of Catheter-related infection including
the tip makes cerebral air embolism a greater risk, therefore bacteremia
left axillary catheters are preferred for the initial attempt, since Diagnostic blood loss
air bubbles passing into the right subclavian artery are more Pseudoaneurysm
likely to traverse the aortic arch. Caution should be exercised Heparin-associated thrombocytopenia
in flushing axillary catheters, which is best accomplished man- Radial artery Cerebral embolization
ually using low pressures and small volumes. Peripheral neuropathy
The axillary artery begins at the lateral border of the first Femoral artery Retroperitoneal hemorrhage
rib as a continuation of the subclavian artery and ends at the Bowel perforation
inferior margin of the teres major muscle, where it becomes Arteriovenous fistula
the brachial artery. The optimal site for catheterization is the Axillary artery Cerebral embolization
junction of the middle and lower third of the vessel, which usu- Brachial plexopathy
ally corresponds to its highest palpable point in the axilla. At Brachial artery Median nerve damage
this point, the artery is superficial and is located at the inferior Cerebral embolization
border of the pectoralis major muscle (Fig. 3.2D). The artery
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Chapter 3: Arterial Line Placement and Care 43

TA B L E 3 . 3 in a sitting patient), injection site, and flush rate. Air embolism


has been cited as a risk mainly for radial arterial catheters but
FACTORS PREDISPOSING TO COMPLICATIONS WITH logically could occur with all arterial catheters, especially ax-
ARTERIAL CANNULATION illary and brachial artery catheters. The risk is minimized by
clearing all air from tubing before flushing, opening the flush
Large tapered cannulas (>20 gauge except at the large valve for no more than 2 to 3 seconds, and avoiding overag-
artery sites) gressive manual flushing of the line.
Hypotension
Coagulopathy
Low cardiac output Diagnostic Blood Loss
Multiple puncture attempts
Use of vasopressors Diagnostic blood loss (DBL) is patient blood loss that occurs
Atherosclerosis due to frequent blood sampling obtained for laboratory testing.
Hypercoagulable state The significance of DBL is underappreciated. It is a particular
Placement by surgical cutdown problem in patients with standard arterial catheter setups that
Site inflammation are used as the site for sampling, because 3 to 5 mL of blood is
Intermittent flushing system typically wasted (to avoid heparin/saline contamination) every
Bacteremia time a sample is obtained. In patients with frequent arterial
blood gas determinations, DBL can be substantial and result
in a transfusion requirement [37]. There are several ways to
minimize DBL, including tubing systems employing a reser-
cannulation. Thrombosis is common with radial and dorsalis voir for blood sampling, continuous intra-arterial blood gas
pedis catheters, but clinical sequelae are rare because of the col- monitoring, point of care microchemistry analysis and the use
lateral circulation [31,32]. When a 20-gauge nontapered Teflon of pediatric collection tubes. Given the expense and risks of
catheter with a continuous 3 mL per hour heparinized-saline blood component therapy, every ICU should have a blood con-
flush is used to cannulate the radial artery for 3 to 4 days, servation policy in place that includes minimizing DBL. Proto-
thrombosis of the vessel can be detected by Doppler study in cols that are designed to optimize laboratory utilization have
5% to 25% of cases [32]. Use of a flush solution containing resulted in significant cost savings and reduced transfusion re-
heparin is no longer standard at our institution because of con- quirements [38].
cern for heparin-induced thrombocytopenia; the incidence of
thrombosis does not appear to be significantly higher using
saline flush [33,34]. Other Mechanical and Technical
Thrombosis often occurs after catheter removal. Women Complications
represent a preponderance of patients who experience flow ab-
normalities following radial artery cannulation, probably be- Other noninfectious complications reported with arterial
cause of smaller arteries and a greater tendency to exhibit va- catheters are pseudoaneurysm formation, hematoma, local ten-
sospasm [23]. Most patients eventually recanalize, generally derness, hemorrhage, neuropathies, and catheter embolization
by 3 weeks after removal of the catheter. Despite the high inci- [17]. Heparin-associated thrombocytopenia (HAT) is a risk of
dence of Doppler-detected thrombosis, clinical ischemia of the any arterial catheter in institutions where heparin is still used
hand is rare and usually resolves following catheter removal. as a standard continuous flush solution [39]. Although heparin
Symptomatic occlusion requiring surgical intervention occurs containing flush solutions may have a slightly reduced rate of
in fewer than 1% of cases, but can be catastrophic with tissue vessel thrombosis and catheter occlusions [40] (especially ra-
loss or amputation of the hand [19]. Most patients who develop dial), in our opinion the risk of HAT outweighs any benefit.
clinical ischemia have an associated contributory cause, such as Our institution has used saline-only flush solutions for many
prolonged circulatory failure with high-dose vasopressor ther- years and we have not noticed an increase in thrombotic or
apy [31]. We consider the femoral artery the most appropriate other complications.
first choice in these patients.
Regular inspection of the extremity for unexplained pain or
signs of ischemia and immediate removal of the catheter mini- Infection
mize significant ischemic complications. If evidence of ischemia
persists after catheter removal, anticoagulation, thrombolytic Infectious sequelae are the most important clinical compli-
therapy, embolectomy, surgical bypass, or cervical sympathetic cations occurring because of arterial cannulation, and many
blockade are treatment options and should be pursued aggres- of the concepts and definitions applied to central venous
sively [19,31]. catheterrelated infection (Chapter 2) are also relevant to arte-
rial catheters.
Catheter-associated infection is usually initiated by skin
Cerebral Embolization flora that invades the intracutaneous tract, causing coloniza-
tion of the catheter, and ultimately, bacteremia. An additional
Continuous flush devices used with arterial catheters are de- source of infection from pressure-monitoring systems is con-
signed to deliver 3 mL per hour of fluid from an infusion bag taminated infusate, which is at greater risk for infection than
pressurized to 300 mm Hg. Lowenstein [35] demonstrated that central venous catheters because (a) the transducer can become
with rapid flushing of radial artery lines with relatively small colonized because of stagnant flow, (b) the flush solution is in-
volumes of radiolabeled solution, traces of the solution could fused at a slow rate (3 mL per hour) and may hang for several
be detected in the central arterial circulation in a time frame days, and (c) multiple blood samples are obtained by several
representative of retrograde flow. Chang [4,36] demonstrated different personnel from stopcocks in the system, which can
that injection of greater than 2 mL of air into the radial artery serve as entry sites for bacteria.
of small primates resulted in retrograde passage of air into the Appreciation of the mechanisms responsible for initiating
vertebral circulation. Factors that increase the risk for retro- arterial catheterrelated infection is important in understand-
grade passage of air are patient size and position (air travels up ing how to minimize infection. Thorough operator and site
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44 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

preparation is paramount and triple barrier protection is ap- 7- to 14-day course of appropriate antibiotics. In complicated
propriate for all larger artery insertions. Chlorhexadine should cases, longer courses are sometimes necessary.
be used for skin preparation [41] and use of a chlorhexidine The optimal evaluation of febrile catheterized patients can
soaked dressing at the insertion site is excellent practice. Breaks be a challenging problem (see Chapter 2). If the site appears ab-
in sterile technique during insertion mandate termination of normal or the patient is in septic shock with no other etiology,
the procedure and replacement of compromised equipment. the catheter should be removed. More specific guidelines are
Nursing personnel should follow strict guidelines when draw- difficult to recommend, and individual factors should always
ing blood samples or manipulating tubing. Blood withdrawn be considered. In general, arterial catheters in place less than 5
to clear the tubing prior to drawing samples should not be rein- days will not be the source of fever unless insertion was contam-
jected unless a specially designed system is in use [42]. Inspec- inated. Catheters in place 7 days or longer should be changed
tion of the site at the start of every nursing shift is mandatory, to a different site given the safety of arterial cannulation and
and the catheter should be removed promptly if abnormalities the small but measurable chance of infection. Guidewire ex-
are noted. Routine change of the pressure monitoring system changes should only be used to change a malfunctioning or
does not reduce infectious complications and may simply be damaged catheter.
another opportunity to introduce colonization.
Historically, it was always felt that arterial catheters had
a lower risk for infection than central venous catheters, but
that is probably no longer true. Impressive reductions in over- RECOMMENDATIONS
all Catheter Related Infections (CRI) have occurred as a result
of increased research, better technology, and an emphasis on Either the radial or femoral artery is an appropriate initial site
patient safety, leading to a convergence of infectious risks for for percutaneous arterial cannulation. Most centers have more
arterial and central venous catheters [43,44]. Using modern experience with radial artery cannulation, but femoral artery
techniques, arterial catheterrelated colonization may occurs catheters are reliable and have a comparable incidence of com-
in up to 5% to 10% of catheters but the incidence of catheter- plication. In our opinion, the femoral artery should be used
related bacteremia should be in the range of 0.5 to 2.0 per first in shocked patients, especially when vasopressors are in-
1,000 catheter-days [15,16,4345]. The site of insertion does fusing, because of the risk of tissue loss with radial or dorsalis
not appear to be an important factor impacting on the inci- pedis catheters. In more than 90% of patients, the radial or
dence of infection [1517,25] but duration is likely important femoral site is adequate to achieve arterial pressure monitor-
[44]. We believe 7 days is an appropriate time to reassess the ing. When these sites are not appropriate, the dorsalis pedis
need for and the location of arterial catheterization [44] but artery is a good alternative, but cannulation is frequently not
each institution should determine its own catheter-associated possible, especially if radial artery cannulation failed because
infection rate so that rational policies can be formulated based of poor perfusion. Under these circumstances, the brachial fol-
on existing local infection rates. lowed by the axillary artery can be safely cannulated; when a
When arterial catheter infection does occur, Staphylococ- coagulopathy is present, ultrasound guidance should be used to
cus species are commonly isolated. Gram-negative organisms avoid complications. Arterial catheters can be left in place until
are less frequent, but predominate in contaminated infusate there is clinical indication to remove them, but infection rate
or equipment-related infection. Infection with Candida species increases proportionally. Iatrogenic anemia and overutilization
is a greater risk in prolonged catheterization of the glucose- of blood tests are a real phenomenon associated with arterial
intolerant patient on multiple systemic broad-spectrum antibi- catheters, which should be discontinued promptly when no
otics. Catheter-associated bacteremia should be treated with a longer required for patient management.

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arterial pressure monitoring: a clinical audit of 1000 studies. Int J Cardiol intensive carean information-based team management approach. Crit Care
5:585, 1984. Med 21:1452, 1993.
28. Macon WL IV, Futrell JW: Median-nerve neuropathy after percutaneous 39. Warkentin TE, Greinacher A: Heparin-induced thrombocytopenia: recog-
puncture of the brachial artery in patients receiving anticoagulants. N Engl nition, treatment, and prevention: the Seventh ACCP Conference on An-
J Med 288:1396, 1973. tithrombotic and Thrombolytic Therapy. Chest 126:311S, 2004.
29. Brown M, Gordon LH, Brown OW, et al: Intravascular monitoring via the 40. Randolph AG, Cook DJ, Gonzales CA, et al: Benefit of heparin in periph-
axillary artery. Anesth Intensive Care 13:38, 1984. eral venous and arterial catheters: systematic review and meta-analysis of
30. Sabik JF, Lytle BW, McCarthy PM, et al: Axillary artery: an alternative site of randomised controlled trials. BMJ 316:969, 1998.
arterial cannulation for patients with extensive aortic and peripheral vascular 41. Mimoz O, Pieroni L, Lawrence C, et al: Prospective, randomized trial of two
disease. J Thorac Cardiovasc Surg 109:885891, 1995. antiseptic solutions for prevention of central venous or arterial catheter colo-
31. Wilkins RG: Radial artery cannulation and ischaemic damage: a review. nization and infection in intensive care unit patients. Crit Care Med 24:1818,
Anaesthesia 40:896, 1985. 1996.
32. Weiss BM, Gattiker RI: Complications during and following radial artery 42. Peruzzi WT, Noskin GA, Moen SG, et al: Microbial contamination of
cannulation: a prospective study. Intensive Care Med 12:424, 1986. blood conservation devices during routine use in the critical care set-
33. Clifton GD, Branson P, Kelly HJ, et al: Comparison of normal saline and ting: results of a prospective, randomized trial. Crit Care Med 24:1157,
heparin solutions for maintenance of arterial catheter patency. Heart Lung 1996.
20:115, 1990. 43. Maki DG, Kluger DM, Crnich CJ. The risk of bloodstream infection in adults
34. Hook ML, Reuling J, Luettgen ML, et al: Comparison of the patency of with different intravascular devices: a systematic review of 200 published
arterial lines maintained with heparinized and nonheparinized infusions. prospective studies. Mayo Clin Proc 81:11591171, 2006.
The Cardiovascular Intensive Care Unit Nursing Research Committee of 44. Lucet JC, Bouadma L, Zahar JR, et al: Infectious risk associated with arterial
St. Lukes Hospital. Heart Lung 16:693, 1987. catheters compared with central venous catheters. Crit Care Med 38:1030
35. Lowenstein E, Little JW 3rd, Lo HH: Prevention of cerebral embolization 1035, 2010.
from flushing radial-artery cannulas. N Engl J Med 285:1414, 1971. 45. Traore O, Liotier J, Souweine B: Prospective study of arterial and central ve-
36. Chang C, Dughi J, Shitabata P, et al: Air embolism and the radial arterial nous catheter colonization and of arterial-and central venous catheter-related
line. Crit Care Med 16:141, 1988. bacteremia in intensive care units. Crit Care Med 33:1276, 2005.

CHAPTER 4 PULMONARY ARTERY


CATHETERS
HARVEY S. REICH

Since their introduction into clinical practice in 1970 by Swan the flow-directed PA catheter, there was no way to assess all
et al. [1], balloon-tipped, flow-directed pulmonary artery (PA) of these by using one instrument in a clinically useful way at
catheters have found widespread use in the clinical manage- bedside. The catheter allows the reflection of right ventricular
ment of critically ill patients. However, in recent years, both (RV) preload (right atrial pressure), RV afterload (PA pressure),
the safety and efficacy of these catheters have been brought left ventricular preloadPA occlusion pressure (PAOP) or pul-
into question. In this chapter, I review the physiologic basis for monary capillary wedge pressure (PCWP)and contractility
their use, some history regarding their development and use, (stroke volume or CO). Left ventricular afterload is reflected
the concerns raised about their use, and suggestions for appro- by the systemic arterial pressure. This information allows the
priate use of the catheters and the information obtained from calculation of numerous parameters, including vascular resis-
them. tances. No other tool allows the gathering of such a large
amount of information.

PHYSIOLOGIC RATIONALE FOR


USE OF THE PULMONARY CONTROVERSIES REGARDING
ARTERY CATHETER USE OF THE PULMONARY
ARTERY CATHETER
In unstable situations, during which hemodynamic changes
often occur rapidly, clinical evaluation may be misleading Despite all of the advantages of the PA catheter, a number of
[2]. PA catheters allow for direct and indirect measure- clinical studies have been published in the past decade that
ment of several major determinants and consequences of car- have shown either no benefit or an increased risk of morbidity
diac performancepreload, afterload, cardiac output (CO) or mortality associated with its use. (See Table 4.1 for a sum-
thereby supplying additional data to aid in clinical decision mary of the evidence for its utility.) Consequently, a number of
making [3]. clinicians have elected to minimize the use of this monitoring
Cardiac function depends on the relationship between mus- device.
cle length (preload), the load on the muscle (afterload), and Furthermore, the relationship of central venous (CV) pres-
the intrinsic property of contractility. Until the development of sure and PA pressure to predict ventricular filling was studied
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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46 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 4 . 1
EVIDENCE BASIS FOR THE PA CATHETER

Authors Year N Design Outcomes

Lower morbidity/mortality
Rao et al. [4] 1983 733/364 Historical controls/cohort Lower mortality
Hesdorffer et al. [5] 1987 61/87 Historical controls/cohort Lower mortality
Shoemaker et al. [6] 1988 146 RCT Lower mortality
Berlauk et al. [7] 1991 89 RCT Lower morbidity
Fleming et al. [8] 1992 33/34 RCT Lower morbidity
Tuchschmidt et al. [9] 1992 26/25 RCT Decreased LOS;
trend toward lower mortality
Boyd et al. [10] 1993 53/54 RCT Lower mortality
Bishop et al. [11] 1995 50/65 RCT Lower mortality
Schiller et al. [12] 1997 53/33/30 Retrospective cohort Lower mortality
Wilson et al. [13] 1999 92/46 RCT Lower mortality
Chang et al. [14] 2000 20/39 Prospective retrospective cohort Lower morbidity
Polonen et al. [15] 2000 196/197 RCT Decreased morbidity
Friese et al. [16] 2006 51379 (no PAC)/ Retrospective analysis of Improved survival in patients
1933 (PAC) National Trauma Data Bank older than 60 or with ISS 2575
and severe shock
No difference
Pearson et al. [17] 1989 226 RCT No difference
Isaacson et al. [18] 1990 102 RCT No difference
Joyce et al. [19] 1990 40 RCT No difference
Yu et al. [20] 1993 35/32 RCT No difference
Gattinoni et al. [21] 1995 252/253/257 RCT No difference
Yu et al. [22] 1995 89 RCT No difference
Durham et al. [23] 1996 27/31 Prospective cohort No difference
Afessa et al. [24] 2001 751 Prospective observational No difference
Rhodes et al. [25] 2002 201 RCT No difference
Richard [26] 2003 676 RCT No difference
Yu et al. [27] 2003 1,010 Prospective cohort No difference
Sandham et al. [28] 2003 997/997 RCT No difference in mortality;
increased risk of pulmonary
embolism in PA group
Sakr et al. [29] 2005 3,147 Observational cohort No difference
Harvey et al. [30] 2005 519/522 RCT No difference in mortality
Binanay et al. [31] 2005 433 RCT No difference in mortality
The National Heart, 2006 513/487 RCT No difference in
Lung and Blood mortality or organ function
Institute ARDS
Clinical Trials Network [32]
Higher or worse morbidity/mortality
Tuman et al. [33] 1989 1094 Controlled prospective cohort Increased ICU stay with PAC
Guyatt [34] 1991 33/148 RCT Higher morbidity
Hayes et al. [35] 1994 50 RCT Higher mortality
Connors et al. [36] 1996 5,735 Prospective cohort Higher mortality
Valentine et al. [37] 1998 60 RCT Increased morbidity
Stewart et al. [38] 1998 133/61 Retrospective cohort Increased morbidity
Ramsey et al. [39] 2000 8,064/5,843 Retrospective cohort Higher mortality
Polanczyk et al. [40] 2001 215/215 Prospective cohort Increased morbidity
Chittock et al. [41] 2004 7,310 Observational cohort Increased mortality in low severity;
decreased mortality in high severity
Peters et al. [42] 2003 360/690 Retrospective case control Increased risk of death
Cohen et al. [43] 2005 26,437/735 Retrospective cohort Increased mortality

ICU, intensive care unit; ISS, injury security score; LOS, length of stay; PA, pulmonary artery; PAC, pulmonary artery catheter; RCT, randomized
control trial.
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Chapter 4: Pulmonary Artery Catheters 47

TA B L E 4 . 2
GENERAL INDICATIONS FOR PULMONARY ARTERY CATHETERIZATION

Management of complicated myocardial infarction


Hypovolemia versus cardiogenic shock
Ventricular septal rupture versus acute mitral regurgitation
Severe left ventricular failure
Right ventricular infarction
Unstable angina
Refractory ventricular tachycardia
Assessment of respiratory distress
Cardiogenic versus noncardiogenic (e.g., acute respiratory distress syndrome)
pulmonary edema
Primary versus secondary pulmonary hypertension
Assessment of shock
Cardiogenic
Hypovolemic
Septic
Pulmonary embolism
Assessment of therapy in selected individuals
Afterload reduction in patients with severe left ventricular function
Inotropic agent
Vasopressors
Beta-blockers
Temporary pacing (ventricular vs. atrioventricular)
Intra-aortic balloon counterpulsation
Mechanical ventilation (e.g., with positive end-expiratory pressure)
Management of postoperative open-heart surgical patients
Assessment of cardiac tamponade/constriction
Assessment of valvular heart disease
Perioperative monitoring of patients with unstable cardiac status during noncardiac surgery
Assessment of fluid requirements in critically ill patients
Gastrointestinal hemorrhage
Sepsis
Acute renal failure
Burns
Decompensated cirrhosis
Advanced peritonitis
Management of severe preeclampsia

Adapted from JM Gore, JS Alpert, JR Benotti, et al: Handbook of Hemodynamic Monitoring. Boston, MA,
Little, Brown, 1984.

in normal volunteers by Kumar et al. [44] who found there was tions in which PA catheterization may be useful are character-
a poor correlation between initial CV pressure and PAOP, with ized by a clinically unclear or rapidly changing hemodynamic
both respective end diastolic ventricular volume and stroke vol- status. Table 4.2 is a partial listing of the indications. Use of
ume indices. Their data call into question the basic tenet of the PA catheters in specific disease entities is discussed in other
theoretical benefit of the PA catheter. chapters.

INDICATIONS FOR PULMONARY CATHETER FEATURES AND


ARTERY CATHETER USE CONSTRUCTION
Clinicians who use a PA catheter for monitoring should under- The catheter is constructed from polyvinylchloride and has a
stand the fundamentals of the insertion technique, the equip- pliable shaft that softens further at body temperature. Because
ment used, and the data that can be generated. The Pulmonary polyvinylchloride has a high thrombogenicity, the catheters are
Artery Catheter Education Program (PACEP) has been devel- generally coated with heparin. Heparin bonding of catheters,
oped by seven specialty organizations, along with the NHLBI introduced in 1981, has been shown to be effective in reduc-
and the FDA and is available at http://www.pacep.org. ing catheter thrombogenicity [45,46] but can cause heparin-
The use of the PA catheter for monitoring has four central induced thrombocytopenia. The standard catheter length is
objectives: (a) to assess left or right ventricular function, or 110 cm, and the most commonly used external diameter is
both, (b) to monitor changes in hemodynamic status, (c) to 5 or 7 French (Fr) (1 Fr = 0.0335 mm). A balloon is fastened
guide treatment with pharmacologic and nonpharmacologic 1 to 2 mm from the tip (Fig. 4.1); when inflated, it guides
agents, and (d) to provide prognostic information. The condi- the catheter (by virtue of fluid dynamic drag) from the greater
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48 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

FIGURE 4.1. Quadruple-lumen pulmonary artery catheter. A: Connection to thermodilution cardiac out-
put computer. B: Connection to distal lumen. C: Connection to proximal lumen. D: Stopcock connected
to balloon at the catheter tip for balloon inflation. E: Thermistor. F: Balloon. Note that the catheter is
marked in 10-cm increments.

intrathoracic veins through the right heart chambers into the (e.g., dopamine, epinephrine) are used. Figure 4.2 shows the
PA. When fully inflated in a vessel of sufficiently large caliber, balloon on the tip inflated.
the balloon protrudes above the catheter tip, thus distributing Several special-purpose PA catheter designs are available.
tip forces over a large area and minimizing the chances for Pacing PA catheters incorporate two groups of electrodes on
endocardial damage or arrhythmia induction during catheter the catheter surface, enabling intracardiac electrocardiographic
insertion (Fig. 4.2). Progression of the catheter is stopped when (ECG) recording or temporary cardiac pacing [48]. These
it impacts in a PA slightly smaller in diameter than the fully in- catheters are used for emergency cardiac pacing, although it is
flated balloon. From this position, the PAOP is obtained. Bal- often difficult to position the catheter for reliable simultaneous
loon capacity varies according to catheter size, and the opera- cardiac pacing and PA pressure measurements. A five-lumen
tor must be aware of the individual balloons maximal inflation catheter allows passage of a specially designed 2.4-Fr bipolar
volume as recommended by the manufacturer. The balloon is pacing electrode (probe) through the additional lumen (located
usually inflated with air, but filtered carbon dioxide should be 19 cm from the catheter tip) and allows emergency temporary
used in any situation in which balloon rupture might result in intracardiac pacing without the need for a separate central ve-
access of the inflation medium to the arterial system (e.g., if a nous puncture. The pacing probe is Teflon coated to allow easy
right-to-left intracardiac shunt or a pulmonary arteriovenous introduction through the pacemaker port lumen; the intracavi-
fistula is suspected). If carbon dioxide is used, periodic deflation tary part of the probe is heparin impregnated to reduce the risk
and reinflation may be necessary, since carbon dioxide diffuses of thrombus formation. One report demonstrated satisfactory
through the latex balloon at a rate of approximately 0.5 cm3 per ventricular pacing in 19 of 23 patients using this catheter de-
minute. Liquids should never be used as the inflation medium. sign (83% success rate) [49]. When a pacing probe is not in
A variety of catheter constructions is available, each use, the fifth lumen may be used for additional central venous
designed for particular clinical applications. Double-lumen access or continuous RV pressure monitoring.
catheters allow balloon inflation through one lumen, and a dis- Continuous mixed venous oxygen saturation measurement
tal opening at the tip of the catheter is used to measure intravas- is clinically available using a fiberoptic five-lumen PA catheter
cular pressures and sample blood. Triple-lumen catheters have [50]. Segal et al. [51] described a catheter that incorpo-
a proximal port terminating 30 cm from the tip of the catheter, rates Doppler technology for continuous CO determinations.
allowing simultaneous measurement of right atrial and PA or Catheters equipped with a fast-response (95 milliseconds)
occlusion pressures. The most commonly used PA catheter in thermistor and intracardiac ECG-monitoring electrodes are
the ICU setting is a quadruple-lumen catheter, which has a lu- also available. These catheters allow determination of the
men containing electrical leads for a thermistor positioned at RV ejection fraction and RV systolic time intervals in criti-
the catheter surface 4 cm proximal to its tip (Fig. 4.1) [47]. The cally ill patients [5255]. The calculated RV ejection fraction
thermistor measures PA blood temperature and allows ther- has correlated well with simultaneous radionuclide first-pass
modilution CO measurements. A five-lumen catheter is also studies [54].
available, with the fifth lumen opening 40 cm from the tip of Aside from the intermittent determination of CO by bo-
the catheter. The fifth lumen provides additional central venous lus administration of cold injectate, PA catheters have been
access for fluid or medication infusions when peripheral access adapted to determine near continuous CO by thermal pulses
is limited or when drugs requiring infusion into a large vein generated by a heating filament on the catheter to produce
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Chapter 4: Pulmonary Artery Catheters 49

FIGURE 4.2. Balloon properly inflated at the tip of a pulmonary artery catheter. Note that the balloon
shields the catheter tip and prevents it from irritating cardiac chambers on its passage to the pulmonary
artery.

temperature changes [56]. The accuracy and reliability of CO Threading the catheter into the PA is more difficult from the
determination by this heatingcooling cycle have been con- basilica, brachial, or femoral vein.
firmed by several studies [5760].

Typical Catheter Insertion Procedure


Pressure Transducers The procedures for typical catheter insertion are as follows:
Hemodynamic monitoring requires a system able to convert 1. Prepare and connect pressure tubing, manifolds, stop-
changes in intravascular pressure into electrical signals suitable cocks, and transducers. Remove the sterile balloon-tipped
for interpretation. The most commonly used hemodynamic catheter from its container. Balloon integrity may be tested
monitoring system is a catheter-tubingtransducer system. A by submerging the balloon in a small amount of fluid and
fluid-filled intravascular catheter is connected to a transducer checking for air leaks as the balloon is inflated (using the
by a fluid-filled tubing system. (For more details, see the dis- amount of air recommended by the manufacturer). Deflate
cussion in Chapters 3 and 26.) the balloon.
2. After a time out, insert a central venous cannula or nee-
dle into the vein as described in Chapter 2. Using the
Seldinger technique, thread the guidewire contained in the
INSERTION TECHNIQUES catheter kit into the vein and remove the catheter or needle
(Figs. 4.3 and 4.4).
General Considerations 3. Make a small incision with a scalpel to enlarge the punc-
ture site (Fig. 4.5). While holding the guidewire stationary,
Manufacturers recommendations should be carefully fol- thread a vessel dilator-sheath apparatus (the size should
lowed. All catheter manufacturers have detailed insertion and be 8 Fr if a 7-Fr catheter is to be used) over the guidewire
training materials. and advance it into the vessel, using a twisting motion to
PA catheterization can be performed in any hospital loca- get through the puncture site (Fig. 4.6). The dilator and
tion where continuous ECG and hemodynamic monitoring are sheath should only be advanced until the tip of the sheath
possible and where equipment and supplies needed for car- is in the vesselestimated by the original depth of the can-
diopulmonary resuscitation are readily available. Fluoroscopy nula or needle required to access the vein. At that point, the
is not essential, but it can facilitate difficult placements. Prop- dilator and guidewire are held stationary and the sheath
erly constructed beds and protective aprons are mandatory for is advance off the dilator into the vessel. Advancing the
safe use of fluoroscopic equipment. Meticulous attention to dilator further may cause great vessel or cardiac damage.
sterile technique is of obvious importance; all involved person- 4. Remove the guidewire and vessel dilator, leaving the intro-
nel must wear sterile caps, gowns, masks, and gloves, and the ducer sheath in the vessel (Fig. 4.7). Suture the sheath in
patient must be fully covered by sterile drapes. place.
The catheter should be inserted percutaneously (not by cut- 5. Pass the proximal portion of the catheter to an assistant
down) into the basilic, brachial, femoral, subclavian, or inter- and have that person attach the stopcock-pressure tubing-
nal jugular veins by using techniques described in Chapter 2. transducer system to the right atrial and PA ports of the
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50 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

FIGURE 4.3. A: Easy blood aspiration has been demonstrated using the guidewire introducer needle. B:
The inner needle is removed. C: The spring guidewire is advanced, soft end first, through the cannula into
the vessel. D: With the guidewire held in place, the cannula is withdrawn from the vessel by being pulled
over and off the length of the guidewire.

PA catheter. Flush the proximal and distal catheter lumens distal end of the sleeve adapter to the introducer sheath
with normal saline. hub.
6. If a sterile sleeve adapter is to be used, insert the catheter 7. Pass the catheter through the introducer sheath into the
through it and pull the adapter proximally over the vein (Fig. 4.8). Advance it, using the marks on the catheter
catheter to keep it out of the way. Once the catheter is shaft indicating 10-cm distances from the tip, until the
advanced to its desired intravascular location, attach the tip is in the right atrium. This requires advancement of

FIGURE 4.4. The spring guidewire, stiff end protruding, is now FIGURE 4.5. A small incision is made with a scalpel to enlarge the
located in the subclavian vein. puncture site.
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Chapter 4: Pulmonary Artery Catheters 51

FIGURE 4.6. A: The vessel dilator-sheath apparatus is threaded over the guidewire and advanced into
the vessel. B: A twisting motion is used to thread the apparatus into the vessel.

FIGURE 4.7. The guidewire and vessel dilator are removed, leaving FIGURE 4.8. The catheter is passed through the introducer sheath
the introducer sheath in the vessel. into the vein.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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52 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

A B

C D E

FIGURE 4.9. A: With the catheter tip in the right atrium, the balloon is inflated. B: The catheter is ad-
vanced into the right ventricle with the balloon inflated, and right ventricle pressure tracings are obtained.
(Center): Waveform tracings generated as the balloon-tipped catheter is advanced through the right heart
chambers into the pulmonary artery. [Adapted from Wiedmann HP, Matthay MA, Matthey RA: Cardio-
vascular pulmonary monitoring in the intensive care unit (Part 1) Chest 85:537;1984, with permission.]
C: The catheter is advanced through the pulmonary valve into the pulmonary artery. A rise in diastolic
pressure should be noted. D: The catheter is advanced to the pulmonary artery occlusion pressure position.
A typical pulmonary artery occlusion pressure tracing should be noted with a and v waves. E: The balloon
is deflated. Phasic pulmonary artery pressure should reappear on the monitor. (See text for details.)
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Chapter 4: Pulmonary Artery Catheters 53

approximately 35 to 40 cm from the left antecubital fossa, to supplement pressure monitoring and checks on balloon
10 to 15 cm from the internal jugular vein, 10 cm from the inflation volumes. An initial cross-table lateral radiograph
subclavian vein, and 35 to 40 cm from the femoral vein. may be obtained in patients on positive end-expiratory
A right atrial waveform on the monitor, with appropriate pressure (PEEP) to rule out superior placements.
fluctuations accompanying respiratory changes or cough,
confirms proper intrathoracic location (Fig. 4.9, center).
If desired, obtain right atrial blood for oxygen saturation Special Considerations
from the distal port. Flush the distal lumen with saline and
record the right atrial pressures. (Occasionally, it is neces- In certain disease states (right atrial or RV dilatation, severe
sary to inflate the balloon to keep the tip from adhering to pulmonary hypertension, severe tricuspid insufficiency, low
the atrial wall during blood aspiration.) CO syndromes), it may be difficult to position a flow-directed
8. With the catheter tip in the right atrium, inflate the bal- catheter properly. These settings may require fluoroscopic guid-
loon with the recommended amount of air or carbon diox- ance to aid in catheter positioning. Infusion of 5 to 10 mL of
ide (Fig. 4.9A). Inflation of the balloon should be associ- cold saline through the distal lumen may stiffen the catheter and
ated with a slight feeling of resistanceif it is not, suspect aid in positioning. Alternatively, a 0.025-cm guidewire 145 cm
balloon rupture and do not attempt further inflation or long may be used to stiffen the catheter when placed through
advancement of the catheter before properly reevaluating the distal lumen of a 7-Fr PA catheter. This manipulation should
balloon integrity. If significant resistance to balloon infla- be performed only under fluoroscopic guidance by an expe-
tion is encountered, suspect malposition of the catheter in rienced operator. Rarely, nonflow-directed PA catheters (e.g.,
a small vessel; withdraw the catheter and readvance it to Cournand catheters) may be required. Because of their rigidity,
a new position. Do not use liquids to inflate the balloon, these catheters have the potential to perforate the right heart
as they might be irretrievable and could prevent balloon and must be placed only under fluoroscopy by a physician ex-
deflation. perienced in cardiac catheterization techniques.
9. With the balloon inflated, advance the catheter until a RV
pressure tracing is seen on the monitor (Fig. 4.9, center).
Obtain and record RV pressures. Catheter passage into PHYSIOLOGIC DATA
and through the RV is an especially risky time in terms
of arrhythmias. Maintaining the balloon inflated in the Measurement of a variety of hemodynamic parameters and
RV minimizes ventricular irritation (Fig. 4.9B), but it is oxygen saturations is possible using the PA catheter. A sum-
important to monitor vital signs and ECG throughout the mary of normal values for these parameters is found in Tables
entire insertion procedure. Elevating the head of the bed to 4.3 and 4.4.
5 degrees and a right tilt position will facilitate the passage
of the catheter through the right ventricle and minimize
the generation of arrhythmias [61]. Pressures
10. Continue advancing the catheter until the diastolic pres-
sure tracing rises above that in the RV (Fig. 4.9, center), Right Atrium
indicating PA placement (Fig. 4.9C). If a RV trace still ap- With the tip of the PA catheter in the right atrium (Fig. 4.9A),
pears after the catheter has been advanced 15 cm beyond the balloon is deflated and a right atrial waveform recorded
the original distance needed to reach the right atrium, sus- (Fig. 4.10). Normal resting right atrial pressure is 0 to 6 mm
pect curling in the ventricle; deflate the balloon, withdraw Hg. Two major positive atrial pressure waves, the a wave and
it to the right atrium, then reinflate it and try again. Ad- v wave, can usually be recorded. On occasion, a third positive
vancement beyond the PA position results in a fall on the wave, the c wave, can also be seen. The a wave is due to atrial
pressure tracing from the levels of systolic pressure noted contraction and follows the simultaneously recorded ECG P
in the RV and PA. When this is noted, record the PAOP wave [62,63]. The a wave peak generally follows the peak of
(Fig. 4.9, center, D) and deflate the balloon. Phasic PA pres-
sure should reappear on the pressure tracing when the bal-
loon is deflated. If it does not, pull back the catheter with
the deflated balloon until the PA tracing appears. With TA B L E 4 . 3
the balloon deflated, blood may be aspirated for oxygen NORMAL RESTING PRESSURES OBTAINED DURING
saturation measurement. Watch for intermittent RV trac- RIGHT HEART CATHETERIZATION
ings indicating slippage of the catheter backward into the
ventricle. Cardiac chamber Pressure (mm Hg)
11. Carefully record the balloon inflation volume needed to
change the PA pressure tracing to the PAOP tracing. If Right atrium
PAOP is recorded with an inflation volume significantly Range 06
lower than the manufacturers recommended volume, or Mean 3
if subsequent PAOP determinations require decreasing
amounts of balloon inflation volume as compared with an Right ventricle
initial appropriate amount, the catheter tip has migrated Systolic 1730
too far peripherally and should be pulled back immedi- Diastolic 06
ately. Pulmonary artery
12. Secure the catheter in the correct PA position by suturing or Systolic 1530
taping it to the skin to prevent inadvertent advancement. Diastolic 513
Apply a transparent dressing with a chlorhexidine sponge Mean 1018
if indicated. Pulmonary artery occlusion (mean) 212
13. Order a chest radiograph to confirm catheter position; the
catheter tip should appear no more than 3 to 5 cm from the Adapted from JM Gore, JS Alpert, JR Benotti, et al: Handbook of
midline. To assess whether peripheral catheter migration Hemodynamic Monitoring. Boston, MA, Little, Brown, 1984.
has occurred, daily chest radiographs are recommended
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54 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 4 . 4
APPROXIMATE NORMAL OXYGEN SATURATION AND CONTENT VALUES

Chamber sampled Oxygen content (vol%) Oxygen saturation (%)

Superior vena cava 14.0 70


Inferior vena cava 16.0 80
Right atrium 15.0 75
Right ventricle 15.0 75
Pulmonary artery 15.0 75
Pulmonary vein 20.0 98
Femoral artery 19.0 96
Atrioventricular oxygen 3.55.5
content difference

Adapted from JM Gore, JS Alpert, JR Benotti, et al: Handbook of Hemodynamic Monitoring. Boston, MA,
Little, Brown, 1984.

the electrical P wave by approximately 80 milliseconds [64]. diastolic volume index and RV ejection fraction can be accu-
The v wave represents the pressure generated by venous filling rately measured [6669].
of the right atrium while the tricuspid valve is closed. The peak
of the v wave occurs at the end of ventricular systole when the Pulmonary Artery
atrium is maximally filled, corresponding to the point near the
end of the T wave on the ECG. The c wave is due to the sud- With the catheter in proper position and the balloon deflated,
den motion of the atrioventricular valve ring toward the right the distal lumen transmits PA pressure (Fig. 4.9E). Normal rest-
atrium at the onset of ventricular systole. The c wave follows ing PA pressure is 15 to 30/5 to 13 mm Hg, with a mean pres-
the a wave by a time equal to the ECG PR interval. The c wave sure of 10 to 18 mm Hg. The PA waveform is characterized by
is more readily visible in cases of PR prolongation [64]. The x a systolic peak and diastolic trough with a dicrotic notch due
descent follows the c wave and reflects atrial relaxation. The y to closure of the pulmonic valve. The peak PA systolic pressure
descent is due to rapid emptying of the atrium after opening occurs in the T wave of a simultaneously recorded ECG.
of the tricuspid valve. The mean right atrial pressure decreases Since the pulmonary vasculature is normally a low-
during inspiration with spontaneous respiration (secondary to resistance circuit, PA diastolic pressure (PADP) is closely re-
a decrease in intrathoracic pressure), whereas the a and v waves lated to mean PAOP (PADP is usually 1 to 3 mm Hg higher
and the x and y descents become more prominent. Once a than mean PAOP) and thus can be used as an index of left ven-
multilumen PA catheter is in position, right atrial blood can tricle filling pressure in patients in whom an occlusion pressure
be sampled and pressure monitored using the proximal lumen. is unobtainable or in whom PADP and PAOP have been shown
It should be noted that the pressures obtained via the proxi- to correlate closely. However, if pulmonary vascular resis-
mal lumen may not accurately reflect right atrial pressure due tance is increased, as in pulmonary embolic disease, pulmonary
to positioning of the lumen against the atrial wall or within fibrosis, or reactive pulmonary hypertension (see Chapter 56),
the introducer sheath. The latter problem is more frequently PADP may markedly exceed mean PAOP and thus become an
encountered in shorter patients [65]. unreliable index of left heart function [64]. Similar provisos ap-
ply when using PA mean pressure as an index of left ventricular
Right Ventricle function.
The normal resting RV pressure is 17 to 30/0 to 6 mm Hg,
recorded when the PA catheter crosses the tricuspid valve (Fig. Pulmonary Artery Occlusion Pressure
4.9B). The RV systolic pressure should equal the PA systolic An important application of the balloon flotation catheter is
pressure (except in cases of pulmonic stenosis or RV outflow the recording of PAOP. This measurement is obtained when
tract obstruction). The RV diastolic pressure should equal the the inflated balloon impacts a slightly smaller branch of the PA
mean right atrial pressure during diastole when the tricuspid (Fig. 4.9D). In this position, the balloon stops the flow, and the
valve is open. Introduction of the catheter with a pacing lumen catheter tip senses pressure transmitted backward through the
allows continuous monitoring of RV hemodynamics when the static column of blood from the next active circulatory bed
pacing wire is not in place. Using special catheters, RV end- the pulmonary veins. Pulmonary venous pressure is a prime de-
terminant of pulmonary congestion and thus of the tendency
for fluid to shift from the pulmonary capillaries into the in-
terstitial tissue and alveoli. Also, pulmonary venous pressure
and PAOP closely reflect left atrial pressure (except in rare in-
stances, such as pulmonary veno-occlusive disease, in which
there is obstruction in the small pulmonary veins), and serve
as indices of left ventricular filling pressure [70,71]. The PAOP
is required to assess left ventricular filling pressure, since mul-
tiple studies have demonstrated that right atrial (e.g., central
venous) pressure correlates poorly with PAOP [72].
The PAOP is a phase-delayed, amplitude-dampened ver-
FIGURE 4.10. Stylized representation of a right atrial waveform in sion of the left atrial pressure. The normal resting PAOP is 2
relation to heart sounds. (See text for discussion of a, c, and v waves to 12 mm Hg and averages 2 to 7 mm Hg below the mean
and x and y descents.) S1 , first heart sound; S2 , second heart sound. PA pressure. The PAOP waveform is similar to that of the
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Chapter 4: Pulmonary Artery Catheters 55

right atrium, with a, c, and v waves and x and y descents


(Fig. 4.10). However, in contradistinction to the right atrial
waveform, the PAOP waveform demonstrates a v wave that is
slightly larger than the a wave [14]. Because of the time required
for left atrial mechanical events to be transmitted through the
pulmonary vasculature, PAOP waveforms are further delayed
when recorded with a simultaneous ECG. The peak of the a
wave follows the peak of the ECG P wave by approximately
240 milliseconds, and the peak of the v wave occurs after the
ECG T wave has been inscribed. Occlusion position is con-
firmed by withdrawing a blood specimen from the distal lu-
men and measuring oxygen saturation. Measured oxygen sat-
uration of 95% or more is satisfactory [71]. The lung segment
from which the sample is obtained will be well ventilated if the
patient breathes slowly and deeply.
A valid PAOP measurement requires a patent vascular chan-
nel between the left atrium and catheter tip. Thus, the PAOP FIGURE 4.11. Pulmonary artery and pulmonary artery occlusion
approximates pulmonary venous pressure (and therefore left tracings with giant v waves distorting with pulmonary artery recording.
atrial pressure) only if the catheter tip lies in zone 3 of the lungs ECG, electrocardiogram.
[62,73]. (The lung is divided into three physiologic zones, de-
pendent on the relationship of PA, pulmonary venous, and alve-
olar pressures. In zone 3, the PA and pulmonary venous pres-
sure exceed the alveolar pressure, ensuring an uninterrupted The position of the catheter can be misinterpreted in patients
column of blood between the catheter tip and the pulmonary with the presence of giant v waves. The most common cause
veins.) If, on portable lateral chest radiograph, the catheter tip of these v waves is mitral regurgitation. During this condition,
is below the level of the left atrium (posterior position in supine left ventricular blood floods a normal-sized, noncompliant left
patients), it can be assumed to be in zone 3. This assumption atrium during ventricular systole, causing giant v waves in the
holds if applied PEEP is less than 15 cm H2 O and the patient occlusion pressure tracing (Fig. 4.11). The giant v wave of mi-
is not markedly volume depleted. Whether the catheter is posi- tral regurgitation may be transmitted to the PA tracing, yielding
tioned in zone 3 may also be determined by certain physiologic a bifid PA waveform composed of the PA systolic wave and the
characteristics (Table 4.5). A catheter occlusion outside zone v wave. As the catheter is occluded, the PA systolic wave is
3 shows marked respiratory variation, an unnaturally smooth lost, but the v wave remains. It is important to note that the
vascular waveform, and misleading high pressures. PA systolic wave occurs earlier in relation to the QRS com-
With a few exceptions [74], estimates of capillary hydro- plex of a simultaneously recorded ECG (between the QRS and
static filtration pressure from PAOP are acceptable [75]. It T waves) than does the v wave (after the T wave).
should be noted that measurement of PAOP does not take into Although a large v wave is not diagnostic of mitral regur-
account capillary permeability, serum colloid osmotic pressure, gitation and is not always present in this circumstance, acute
interstitial pressure, or actual pulmonary capillary resistance mitral regurgitation remains the most common cause of giant
[75,76]. These factors all play roles in the formation of pul- v waves in the PAOP tracing. Prominent v waves may occur
monary edema, and the PAOP should be interpreted in the whenever the left atrium is distended and noncompliant due
context of the specific clinical situation. to left ventricular failure from any cause (e.g., ischemic heart
Mean PAOP correlates well with left ventricular end- disease, dilated cardiomyopathy) [77,78] or secondary to the
diastolic pressure (LVEDP), provided the patient has a normal increased pulmonary blood flow in acute ventricular septal de-
mitral valve and normal left ventricular function. In myocar- fect [79]. Acute mitral regurgitation is the rare instance when
dial infarction, conditions with decreased left ventricular com- the PA end-diastolic pressure may be lower than the computer-
pliance (e.g., ischemia, left ventricular hypertrophy), and con- measured mean occlusion pressure [64].
ditions with markedly increased left ventricular filling pressure End expiration provides a readily identifiable reference
(e.g., dilated cardiomyopathy), the contribution of atrial con- point for PAOP interpretation because pleural pressure returns
traction to left ventricular filling is increased. Thus, the LVEDP to baseline at the end of passive deflation (approximately equal
may be significantly higher than the mean left atrial pressure to atmospheric pressure). Pleural pressure can exceed the nor-
or PAOP [62]. mal resting value with active expiratory muscle contraction or

TA B L E 4 . 5
CHECKLIST FOR VERIFYING POSITION OF PULMONARY ARTERY CATHETER

Zone 3 Zone 1 or 2

PAOP contour Cardiac ripple (A + V waves) Unnaturally smooth


PAD versus PAOP PAD > PAOP PAD < PAOP
PEEP trial PAOP < 1/2 PEEP PAOP > 1/2 PEEP
Respiratory variation of PAOP < 1/2 PALV 1/2 PALV
Catheter-tip location LA level or below Above LA level

LA, left atrium; PAD, pulmonary artery diastolic pressure; PALV , alveolar pressure; PAOP, pulmonary artery
occlusion pressure; PEEP, positive end-expiratory pressure.
Adapted from RJ Schultz, GF Whitfield, JJ LaMura, et al: The role of physiologic monitoring in patients
with fractures of the hip. J Trauma 25:309, 1985.
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56 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

use of PEEP. How much PEEP is transmitted to the pleural is adequate), the resultant cooling curve recorded at a down-
space cannot be estimated easily, since it varies depending on stream site allows calculation of net blood flow. CO is inversely
lung compliance and other factors. When normal lungs deflate proportional to the integral of the time-versus-temperature
passively, end-expiratory pleural pressure increases by approx- curve.
imately one half of the applied PEEP. In patients with reduced In practice, a known amount of cold or room temperature
lung compliance (e.g., patients with acute respiratory distress solution (typically 10 mL of 0.9% saline in adults and 5 mL of
syndrome; ARDS), the transmitted fraction may be one-fourth 0.9% saline in children) is injected into the right atrium via the
or less of the PEEP value. In the past, PEEP levels greater than catheters proximal port. The thermistor allows recording of
10 mm Hg were thought to interrupt the column of blood be- the baseline PA blood temperature and subsequent temperature
tween the left atrium and PA catheter tip, causing the PAOP to change. The resulting curve is usually analyzed by computer,
reflect alveolar pressure more accurately than left atrial pres- although it can be analyzed manually by simple planimetric
sure. However, two studies suggest that this may not hold true methods. Correction factors are added by catheter manufac-
in all cases. Hasan et al. [80] concluded that the PAOP left turers to account for the mixture of cold indicator with warm
atrial fluid column was protected by lung injury, and Teboul residual fluid in the catheter injection lumen and the heat trans-
et al. [81] could find no significant discrepancy between PAOP fer from the catheter walls to the cold indicator.
and simultaneously measured LVEDP at PEEP levels of 0, 10, Reported coefficients of variation using triplicate determi-
and 16 to 20 cm H2 O in patients with ARDS. They hypothesize nations, using 10 mL of cold injectate and a bedside computer,
that (a) a large intrapulmonary right-to-left shunt may provide are approximately 4% or less. Variations in the rate of injec-
a number of microvessels shielded from alveolar pressure, al- tion can also introduce error into CO determinations, and it
lowing free communication from PA to pulmonary veins, or (b) is thus important that the solution be injected as rapidly as
in ARDS, both vascular and lung compliance may decrease, possible. Careful attention must be paid to the details of this
reducing transmission of alveolar pressure to the pulmonary procedure; even then, changes of less than 10% to 15% above
microvasculature and maintaining an uninterrupted blood col- or below an initial value may not truly establish directional va-
umn from the catheter tip to the left atrium. lidity. Thermodilution CO is inaccurate in low-output states,
Although it is difficult to estimate precisely the true transmu- tricuspid regurgitation, and in cases of atrial or ventricular sep-
ral vascular pressure in a patient on PEEP, temporarily discon- tal defects [84].
necting PEEP to measure PAOP is not recommended. Because Normal values for arterialvenous oxygen content differ-
the hemodynamics have been destabilized, these measurements ence, mixed venous oxygen saturation, and CO can be found
will be of questionable value. Venous return increases acutely in Table 4.6.
after discontinuation of PEEP [81], and abrupt removal of
PEEP will cause hypoxia, which may not reverse quickly on Analysis of Mixed Venous Blood
reinstitution of PEEP [82]. Additional discussion of measure-
ment and interpretation of pulmonary vascular pressures on CO can be approximated merely by examining mixed venous
PEEP is found in Chapter 58. (PA) oxygen saturation. Theoretically, if CO rises, then the
mixed venous oxygen partial pressure will rise, since peripheral
tissues need to exact less oxygen per unit of blood. Conversely,
if CO falls, peripheral extraction from each unit will increase
Cardiac Output to meet the needs of metabolizing tissues. Serial determinations
of mixed venous oxygen saturation may display trends in CO.
Normal mixed venous oxygen saturation is 70% to 75%; val-
Thermodilution Technique ues of less than 60% are associated with heart failure and values
A catheter equipped with a thermistor 4 cm from its tip al- of less than 40% with shock [85]. Potential sources of error in
lows calculation of CO by using the thermodilution principle this determination include extreme low-flow states where poor
[47,83]. The thermodilution principle holds that if a known mixing may occur, contamination of desaturated mixed venous
quantity of cold solution is introduced into the circulation and blood by saturated pulmonary capillary blood when the sam-
adequately mixed (passage through two valves and a ventricle ple is aspirated too quickly through the nonwedged catheter

TA B L E 4 . 6
SELECTED HEMODYNAMIC VARIABLES DERIVED FROM RIGHT HEART
CATHETERIZATION

Hemodynamic variable Normal range

Arterialvenous content difference 3.55.5 mL/100 mL


Cardiac index 2.54.5 L/min/m2
Cardiac output 3.07.0 L/min
Left ventricular stroke work index 4560 g/beat/m2
Mixed venous oxygen content 18.0 mL/100 mL
Mixed venous saturation 75% (approximately)
Oxygen consumption 200250 mL/min
Pulmonary vascular resistance 120250 dynes/sec/cm5
Stroke volume 70130 mL/contraction
Stroke volume index 4050 mL/contraction/m2
Systemic vascular resistance 1,1001,500 dynes/sec/cm2

Adapted from JM Gore, JS Alpert, JR Benotti, et al: Handbook of Hemodynamic Monitoring. Boston, MA,
Little, Brown, 1984.
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Chapter 4: Pulmonary Artery Catheters 57

TA B L E 4 . 7
HEMODYNAMIC PARAMETERS IN COMMONLY ENCOUNTERED CLINICAL SITUATIONS (IDEALIZED)

RA RV PA PAOP AO CI SVR PVR

Normal 06 25/06 25/612 612 130/80 2.5 1,500 250


Hypovolemic shock 02 1520/02 1520/26 26 90/60 <2.0 >1,500 250
Cardiogenic shock 8 50/8 50/35 35 90/60 <2.0 >1,500 250
Septic shock
Early 02 2025/02 2025/06 06 90/60 2.5 <1,500 <250
Latea 04 25/410 25/410 410 90/60 <2.0 >1,500 >250
Acute massive pulmonary embolism 812 50/12 50/1215 12 90/60 <2.0 >1,500 >450
Cardiac tamponade 1218 25/1218 25/1218 1218 90/60 <2.0 >1,500 250
AMI without LVF 06 25/06 25/1218 18 140/90 2.5 1,500 250
AMI with LVF 06 3040/06 3040/1825 >18 140/90 >2.0 >1,500 >250
Biventricular failure secondary to LVF >6 5060/ >6 5060/25 1825 120/80 2.0 >1,500 >250
RVF secondary to RVI 1220 30/1220 30/12 <12 90/60 <2.0 >1,500 >250
Cor pulmonale >6 80/ >6 80/35 <12 120/80 2.0 >1,500 >400
Idiopathic pulmonary hypertension 06 80100/06 80100/40 <12 100/60 <2.0 >1,500 >500
Acute ventricular septal ruptureb 6 60/68 60/35 30 90/60 <2.0 >1,500 >250
a
Hemodynamic profile seen in approximately one third of patients in late septic shock.
b
Confirmed by appropriate RAPA oxygen saturation step-up. See text for discussion.
AMI, acute myocardial infarction; AO, aortic; CI, cardiac index; LVF, left ventricular failure; PA, pulmonary artery; PAOP, pulmonary artery occlusion
pressure; PVR, pulmonary vascular resistance; RA, right atrium; RV, right ventricle; RVF, right ventricular failure; RVI, right ventricular infarction; SVR,
systemic vascular resistance.
Adapted from Gore JM, Alpert JS, Benotti JR, et al: Handbook of Hemodynamic Monitoring. Boston, MA, Little, Brown, 1984.

[86] or in certain disease states (e.g., sepsis) where microcircu- cular basis to explain abnormal symptoms or signs and as a
latory shunting may occur. Fiberoptic reflectance oximetry PA baseline to gauge a patients disease progression or response to
catheters can continuously measure and record mixed venous therapy. Right atrial pressures of 0 to 6 mm Hg, PA systolic
oxygen saturations in appropriate clinical situations [50,87]. pressures of 15 to 30 mm Hg, PADPs of 5 to 12 mm Hg, PA
mean pressures of 9 to 18 mm Hg, PAOP of 5 to 12 mm Hg, and
a cardiac index exceeding 2.5 L per minute per m2 characterize
Derived Parameters a normal cardiovascular state at rest.
Table 4.7 summarizes specific hemodynamic patterns for a
Useful hemodynamic parameters that can be derived using data variety of disease entities in which PA catheters have been indi-
with PA catheters include the following: cated and provide clinical information that can impact patient
care.
1. Cardiac index = CO (L/minute)/BSA (m2 )
2. Stroke volume = CO (L/minute)/heart rate (beats/minute)
3. Stroke index = CO (L/minute)/[heart rate (beats/minute)
BSA (m2 )]
COMPLICATIONS
4. Mean arterial pressure (mmHg) = [(2 diastolic) + Minor and major complications associated with bedside bal-
systolic]/3 loon flotation PA catheterization have been reported (Table
5. Systemic vascular resistance (dyne/second/cm5 ) = ([mean 4.8). During the 1970s, in the first 10 years of clinical catheter
arterial pressure mean right atrial pressure (mm Hg)] use, a number of studies reported a relatively high incidence
80)/CO (L/minute) of certain complications. Consequent revision of guidelines for
6. Pulmonary arteriolar resistance (dyne/second/cm5 ) = PA catheter use and improved insertion and maintenance tech-
([mean PA pressure PAOP (mm Hg)] 80)/CO (L/minute) niques resulted in a decreased incidence of these complications
7. Total pulmonary resistance (dyne/second/cm5 ) = ([mean
PA pressure (mm Hg)] 80)/CO (L/minute)
8. Left ventricular stroke work index = 1.36 (mean arterial TA B L E 4 . 8
pressure PAOP) stroke index/100
9. Do2 (mL/minute/m2 ) = cardiac index arterial O2 content COMPLICATIONS OF PULMONARY ARTERY
10 CATHETERIZATION
Normal values are listed in Table 4.6. Associated with central venous access
Balloon rupture
Knotting
CLINICAL APPLICATIONS OF THE Pulmonary infarction
Pulmonary artery perforation
PULMONARY ARTERY CATHETER Thrombosis, embolism
Arrhythmias
Normal Resting Hemodynamic Profile Intracardiac damage
Infections
The finding of normal CO associated with normal left and right Miscellaneous complications
heart filling pressures is useful in establishing a noncardiovas-
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58 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

in the 1980s [88]. The majority of complications are avoid- in an attempt to restore an apparently damped pressure trace.
able by scrupulous attention to detail in catheter placement Pulmonary embolic phenomena resulting from thrombus for-
and maintenance. mation around the catheter or over areas of endothelial damage
can also result in pulmonary infarction.
The reported incidence of pulmonary infarction secondary
Complications Associated with Central to PA catheters in 1974 was 7.2% [101], but recently reported
rates of pulmonary infarction are much lower. Boyd et al. [103]
Venous Access found a 1.3% incidence of pulmonary infarction in a prospec-
tive study of 528 PA catheterizations. Sise et al. [104] reported
The insertion techniques and complications of central venous
no pulmonary infarctions in a prospective study of 319 PA
cannulation are discussed in Chapter 2. Reported local vascu-
catheter insertions. Use of continuous saline flush solutions and
lar complications include local arterial or venous hematomas,
careful monitoring of PA waveforms are important reasons for
unintentional entry of the catheter into the carotid system, atri-
the decreased incidence of this complication.
oventricular fistulas, and pseudoaneurysm formation [8991].
Adjacent structures, such as the thoracic duct, can be damaged,
with resultant chylothorax formation. Pneumothorax can be
a serious complication of insertion, although the incidence is Pulmonary Artery Perforation
relatively low (1% to 2%) [64,89,92]. The incidence of pneu-
A serious and feared complication of PA catheterization is rup-
mothorax is higher with the subclavian approach than with the
ture of the PA leading to hemorrhage, which can be massive and
internal jugular approach in some reports [93], but other stud-
sometimes fatal [105107]. Rupture may occur during inser-
ies demonstrate no difference between the two sites [94,95].
tion or may be delayed a number of days [107]. PA rupture or
The incidence of complications associated with catheter inser-
perforation has been reported in approximately 0.1% to 0.2%
tion is generally considered to be inversely proportional to the
of patients [93,108,109], although recent pathologic data sug-
operators experience.
gest the true incidence of PA perforation is somewhat higher
[110]. Proposed mechanisms by which PA rupture can occur in-
clude (a) an increased pressure gradient between PAOP and PA
Balloon Rupture pressure brought about by balloon inflation and favoring distal
catheter migration, where perforation is more likely to occur;
Balloon rupture occurred more frequently in the early 1970s (b) an occluded catheter tip position favoring eccentric or dis-
than it does now and was generally related to exceeding rec- tended balloon inflation with a spearing of the tip laterally and
ommended inflation volumes. The main problems posed by through the vessel; (c) cardiac pulsation causing shearing forces
balloon rupture are air emboli gaining access to the arterial and damage as the catheter tip repeatedly contacts the vessel
circulation and balloon fragments embolizing to the distal pul- wall; (d) presence of the catheter tip near a distal arterial bifur-
monary circulation. If rupture occurs during catheter insertion, cation where the integrity of the vessel wall against which the
the loss of the balloons protective cushioning function can pre- balloon is inflated may be compromised; and (e) simple lateral
dispose to endocardial damage and attendant thrombotic and pressure on vessel walls caused by balloon inflation (this tends
arrhythmic complications. to be greater if the catheter tip was occluded before inflation be-
gan). Patient risk factors for PA perforation include pulmonary
hypertension, mitral valve disease, advanced age, hypothermia,
Knotting and anticoagulant therapy. In patients with these risk factors
and in whom PADP reflects PAOP reasonably well, avoidance
Knotting of a catheter around itself is most likely to occur when of subsequent balloon inflation altogether constitutes prudent
loops form in the cardiac chambers and the catheter is repeat- prophylaxis.
edly withdrawn and readvanced [96]. Knotting is avoided if Another infrequent but life-threatening complication is false
care is taken not to advance the catheter significantly beyond aneurysm formation associated with rupture or dissection of
the distances at which entrance to the ventricle or PA would the PA [111]. Technique factors related to PA hemorrhage are
ordinarily be anticipated. Knotted catheters usually can be ex- distal placement or migration of the catheter; failure to remove
tricated transvenously; guidewire placement [97], venotomy, or large catheter loops placed in the cardiac chambers during in-
more extensive surgical procedures are occasionally necessary. sertion; excessive catheter manipulation; use of stiffer catheter
Knotting of PA catheters around intracardiac structures [98] designs; and multiple overzealous or prolonged balloon infla-
or other intravascular catheters [99] has been reported. Rarely, tions. Adherence to strict technique may decrease the incidence
entrapment of a PA catheter in cardiac sutures after open-heart of this complication. In a prospective study reported in 1986,
surgery has been reported, requiring varying approaches for no cases of PA rupture occurred in 1,400 patients undergoing
removal [100]. PA catheterization for cardiac surgery [94].
PA perforation typically presents with massive hemoptysis.
Emergency management includes immediate occlusion arteri-
Pulmonary Infarction ogram and bronchoscopy, intubation of the unaffected lung,
and consideration of emergency lobectomy or pneumonec-
Peripheral migration of the catheter tip (caused by catheter tomy. PA catheter balloon tamponade resulted in rapid control
softening and loop tightening over time) with persistent, unde- of bleeding in one case report [112]. Application of PEEP to
tected wedging in small branches of the PA is the most common intubated patients may also tamponade hemorrhage caused by
mechanism underlying pulmonary ischemic lesions attributable a PA catheter [113,114].
to PA catheters [101]. These lesions are usually small and
asymptomatic, often diagnosed solely on the basis of changes
in the chest radiograph demonstrating an occlusion-shaped Thromboembolic Complications
pleural-based density with a convex proximal contour [102].
Severe infarctions are usually produced if the balloon is left Because PA catheters constitute foreign bodies in the cardio-
inflated in the occlusion position for an extended period, thus vascular system and can potentially damage the endocardium,
obstructing more central branches of the PA, or if solutions are they are associated with an increased incidence of thrombo-
injected at relatively high pressure through the catheter lumen sis. Thrombi encasing the catheter tip and aseptic thrombotic
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Chapter 4: Pulmonary Artery Catheters 59

vegetations forming at endocardial sites in contact with the plete heart block during catheter insertion, and some have ad-
catheter have been reported [103,115]. Extensive clotting vocated the insertion of a temporary transvenous pacing wire,
around the catheter tip can occlude the pulmonary vasculature a PA catheter with a pacing lumen, or pacing PA catheter with
distal to the catheter, and thrombi anywhere in the venous sys- the pacing leads on the external surface of the catheter [129].
tem or right heart can serve as a source of pulmonary emboli. However, use of an external transthoracic pacing device should
Subclavian venous thrombosis, presenting with unilateral neck be sufficient to treat this complication.
vein distention and upper extremity edema, may occur in up
to 2% of subclavian placements [116,117]. Venous thrombo-
sis complicating percutaneous internal jugular vein catheter- Intracardiac Damage
ization is fairly commonly reported, although its clinical
importance remains uncertain [118]. Consistently damped Damage to the right heart chambers, tricuspid valve, pul-
pressure tracings without evidence of peripheral catheter mi- monic valve, and their supporting structures as a consequence
gration or pulmonary vascular occlusion should arouse suspi- of PA catheterization has been reported [130133]. The re-
cion of thrombi at the catheter tip. A changing relationship of ported incidence of catheter-induced endocardial disruption
PADP to PAOP over time should raise concern about possible detected by pathologic examination varies from 3.4% [115] to
pulmonary emboli. 75% [134], but most studies suggest a range of 20% to 30%
If an underlying hypercoagulable state is known to exist, if [117,131,132]. These lesions consist of hemorrhage, sterile
catheter insertion was particularly traumatic, or if prolonged thrombus, intimal fibrin deposition, and nonbacterial throm-
monitoring becomes necessary, one should consider cautiously botic endocarditis. Their clinical significance is not clear, but
anticoagulating the patient. there is concern that they may serve as a nidus for infectious
Heparin-bonded catheters reduce thrombogenicity [45] and endocarditis.
are commonly used. However, an important complication of Direct damage to the cardiac valves and supporting chordae
heparin-bonded catheters is heparin-induced thrombocytope- occurs primarily by withdrawal of the catheters while the bal-
nia (HIT) [119,120]. Routine platelet counts are recommended loon is inflated [1]. However, chordal rupture has been reported
for patients with heparin-bonded catheters in place. Because despite balloon deflation [113]. The incidence of intracardiac
of the risk of HIT, some hospitals have abandoned the use of and valvular damage discovered on postmortem examination
heparin-bonded catheters. is considerably higher than that of clinically significant valvular
dysfunction.

Rhythm Disturbances Infections


Atrial and ventricular arrhythmias occur commonly during in- Catheter-related septicemia (the same pathogen growing from
sertion of PA catheters [121]. Premature ventricular contrac- blood and the catheter tip) was reported in up to 2% of pa-
tions occurred during 11% of the catheter insertions originally tients undergoing bedside catheterization in the 1970s [135].
reported by Swan et al. [1]. However, the incidence of septicemia related to the catheter ap-
Studies have reported advanced ventricular arrhythmias pears to have declined in recent years, with a number of studies
(three or more consecutive ventricular premature beats) in ap- suggesting a septicemia rate of 0% to 1% [93,136,137]. In situ
proximately 30% to 60% of patients undergoing right heart time of more than 72 to 96 hours significantly increases the
catheterization [93,117,122124]. Most arrhythmias are self- risk of catheter-related sepsis. Right-sided septic endocarditis
limited and do not require treatment, but sustained ventricular has been reported [133,138], but the true incidence of this com-
arrhythmias requiring treatment occur in 0% to 3% of pa- plication is unknown. Becker et al. [130] noted two cases of
tients [103,123,124]. Risk factors associated with increased left ventricular abscess formation in patients with PA catheters
incidence of advanced ventricular arrhythmias are acute my- and Staphylococcus aureus septicemia. Incidence of catheter
ocardial ischemia or infarction, hypoxia, acidosis, hypocal- colonization or contamination varies from 5% to 20%, de-
cemia, and hypokalemia [92,123]. A right lateral tilt position pending on the duration of catheter placement and the criteria
(5-degree angle) during PA catheter insertion is associated with used to define colonization [137139]. In situ catheter-related
a lower incidence of malignant ventricular arrhythmias than is bloodstream infection may be diagnosed by either differential
the Trendelenburg position [61]. time to positivity or quantitative blood cultures [140]. With
Although the majority of arrhythmias occur during catheter the former method, paired blood cultures are drawn from a
insertion, arrhythmias may develop at any time after the peripheral vein and the catheter. If the catheter blood culture
catheter has been correctly positioned. These arrhythmias are turns positive two or more hours sooner than the peripheral
due to mechanical irritation of the conducting system and may blood culture, the catheter is the likely cause of the bacteremia.
be persistent. Ventricular ectopy may also occur if the catheter With the other method, positive quantitative blood cultures
tip falls back into the RV outflow tract. Evaluation of catheter- drawn from the catheter are sensitive, specific, and predictive
induced ectopy should include a portable chest radiograph to of catheter-related bacteremia [141].
evaluate catheter position and assessment of the distal lumen Pressure transducers have also been identified as an occa-
pressure tracing to ensure that the catheter has not slipped into sional source of infection [142]. The chance of introducing
the RV. Lidocaine may be used but is unlikely to ablate the ec- infection into a previously sterile system is increased during in-
topy because the irritant is not removed [125]. If the arrhythmia jections for CO determinations and during blood withdrawal.
persists after lidocaine therapy or is associated with hemody- Approaches to reduce the risk of catheter-related infection in-
namic compromise, the catheter should be removed. Catheter clude use of a sterile protective sleeve and antibiotic bonding
removal should be performed by physicians under continuous to the catheter [94,143,144]. Scheduled changes of catheters
ECG monitoring, since the ectopy occurs almost as frequently do not reduce the rate of infection [145].
during catheter removal as during insertion [126,127].
Right bundle branch block (usually transient) can also com-
plicate catheter insertion [128]. Patients undergoing anesthesia Other Complications
induction, those in the early stages of acute anteroseptal my-
ocardial infarction, and those with acute pericarditis appear Rare miscellaneous complications that have been reported in-
particularly susceptible to this complication. Patients with pre- clude (a) hemodynamically significant decreases in pulmonary
existing left bundle branch block are at risk for developing com- blood flow caused by balloon inflation in the central PA in
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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60 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

postpneumonectomy patients with pulmonary hypertension in after each PAOP recording. There is never an indication
the remaining lung [146], (b) disruption of the catheters in- for continuous PAOP monitoring.
traluminal septum as a result of injecting contrast medium un- b. Constant pressure monitoring is required each time the
der pressure [147], (c) artifactual production of a midsystolic balloon is inflated. It should be inflated slowly, in small
click caused by a slapping motion of the catheter against the increments, and must be stopped as soon as the pressure
interventricular septum in a patient with RV strain and para- tracing changes to PAOP or damped.
doxic septal motion [148], (d) thrombocytopenia secondary c. If an occlusion is recorded with balloon volumes signif-
to heparin-bonded catheters [119,120], and (e) dislodgment of icantly less than the inflation volume recommended on
pacing electrodes [149]. Multiple unusual placements of PA the catheter shaft, withdraw the catheter to a position
catheters have also been reported, including in the left peri- where full (or nearly full) inflation volume produces the
cardiophrenic vein, via the left superior intercostal vein into desired trace.
the abdominal vasculature, and from the superior vena cava d. Anticipate catheter tip migration. Softening of the
through the left atrium and left ventricle into the aorta after catheter material with time, repeated manipulations, and
open-heart surgery [150152]. cardiac motion make distal catheter migration almost in-
evitable.
i. Continuous PA pressure monitoring is mandatory,
and the trace must be closely watched for changes
GUIDELINES FOR SAFE USE OF from characteristic PA pressures to those indicating
PULMONARY ARTERY a PAOP or damped tip position.
ii. Decreases over time in the balloon inflation volumes
CATHETERS necessary to attain occlusion tracings should raise
suspicion regarding catheter migration.
Multiple revisions and changes in emphasis to the original iii. Confirm satisfactory tip position with chest radio-
recommended techniques and guidelines have been published graphs immediately after insertion and at least daily.
[88,153,154]. These precautions are summarized as follows: e. Do not use liquids to inflate the balloon. They may pre-
vent deflation, and their relative incompressibility may
1. Avoiding complications associated with catheter insertion. increase lateral forces and stress on the walls of pul-
a. Inexperienced personnel performing insertions must be monary vessels.
supervised. Many hospitals require that PA catheters be f. Hemoptysis is an ominous sign and should prompt an
inserted by a fully trained intensivist, cardiologist, or urgent diagnostic evaluation and rapid institution of ap-
anesthesiologist. Use of ultrasound guidance is recom- propriate therapy.
mended. g. Avoid injecting solutions at high pressure through the
b. Keep the patient as still as possible. Restraints or sedation catheter lumen on the assumption that clotting is the
may be required but the patient should be fully monitored cause of the damped pressure trace. First, aspirate from
with ECG and pulse oximetry. the catheter. Then consider problems related to catheter
c. Strict sterile technique is mandatory. A chlorhexidine position, stopcock position, transducer dome, transduc-
skin prep solution and maximum barrier precautions are ers, pressure bag, flush system, or trapped air bubbles.
recommended. Never flush the catheter in the occlusion position.
d. Examine the postprocedure chest radiograph for pneu- 5. Avoiding thromboembolic complications.
mothorax (especially after subclavian or internal jugular a. Minimize trauma induced during insertion.
venipuncture) and for catheter tip position. b. Consider the judicious use of anticoagulants in patients
2. Avoiding balloon rupture. with hypercoagulable states or other risk factors.
a. Always inflate the balloon gradually. Stop inflation if no c. Avoid flushing the catheter under high pressure.
resistance is felt. d. Watch for a changing PADPPAOP relationship, as well
b. Do not exceed recommended inflation volume. At the as for other clinical indicators of pulmonary embolism.
recommended volume, excess air will automatically be 6. Avoiding arrhythmias.
expelled from a syringe with holes bored in it that is con- a. Constant ECG monitoring during insertion and main-
stantly attached to the balloon port. Maintaining recom- tenance, as well as ready accessibility of all supplies
mended volume also helps prevent the accidental injec- for performing cardiopulmonary resuscitation, defibril-
tion of liquids. lation, and temporary pacing, are mandatory.
c. Keep the number of inflationdeflation cycles to a mini- b. Use caution when catheterizing patients with an acutely
mum. ischemic myocardium or preexisting left bundle branch
d. Do not reuse catheters designed for single usage, and do block.
not leave catheters in place for prolonged periods. c. When the balloon is deflated, do not advance the catheter
e. Use carbon dioxide as the inflation medium if communi- beyond the right atrium.
cation between the right and left sides of the circulation d. Avoid over manipulation of the catheter.
is suspected. e. Secure the introducer in place at the insertion site.
3. Avoiding knotting. Discontinue advancement of the catheter f. Watch for intermittent RV pressure tracings when the
if entrance to right atrium, RV, or PA has not been achieved catheter is thought to be in the PA position. An unex-
at distances normally anticipated from a given insertion site. plained ventricular arrhythmia in a patient with a PA
If these distances have already been significantly exceeded, catheter in place indicates the possibility of catheter-
or if the catheter does not withdraw easily, use fluoroscopy provoked ectopy.
before attempting catheter withdrawal. Never pull force- 7. Avoiding valvular damage.
fully on a catheter that does not withdraw easily. a. Avoid prolonged catheterization and excessive manipu-
4. Avoiding damage to pulmonary vasculature and paren- lation.
chyma. b. Do not withdraw the catheter when the balloon is in-
a. Keep recording time of PAOP to a minimum, particularly flated.
in patients with pulmonary hypertension and other risk 8. Avoiding infections.
factors for PA rupture. Be sure the balloon is deflated a. Use meticulously sterile technique on insertion.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 4: Pulmonary Artery Catheters 61

b. Avoid excessive number of CO determinations and blood concludes that the use of the PA catheter neither increased over-
withdrawals. all mortality or hospital days nor conferred benefit. The authors
c. Avoid prolonged catheterization. conclude that despite nearly 20 years of randomized clinical tri-
d. Remove the catheter if signs of phlebitis develop. Culture als involving the PA catheter, there has not been a clear strategy
the tip and use antibiotics as indicated. in its use which has lead to improved survival [155].
Although there are open trials involving the PA catheter
listed in the clinical trials registry, these are focused on ele-
SUMMARY ments of catheter data interpretation or comparisons of hemo-
dynamics obtained from the PA catheter to other methods of
Hemodynamic monitoring enhances the understanding of obtaining these measurements [156]. There are no further ran-
cardiopulmonary pathophysiology in critically ill patients. domized clinical trials looking at the PA catheter and patient
Nonetheless, the risk-to-benefit profile of PA catheterization in outcomes recruiting patients at this time.
various clinical circumstances remains uncertain. Recent large Until the results of future studies are available, clinicians us-
trials have concluded that there may be no outcome benefit to ing hemodynamic monitoring should carefully assess the risk-
patients with PA catheters used as part of clinical decision mak- to-benefit ratio on an individual patient basis. The operator
ing. There is increasing concern that PA catheterization may be should understand the indications, insertion techniques, equip-
overused and that the data obtained may not be optimally used, ment, and data that can be generated before undertaking PA
or perhaps in specific groups may increase morbidity and mor- catheter insertion. PA catheterization must not delay or replace
tality. A recent meta-analysis of 13 randomized clinical trials bedside clinical evaluation and treatment.

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Chapter 4: Pulmonary Artery Catheters 63

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108. McDaniel DD, Stone JG, Faltas AN, et al: Catheter induced pulmonary 133. Rowley KM, Clubb KS, Smith GJW, et al: Right sided infective endocarditis
artery hemorrhage: diagnosis and management in cardiac operations. J Tho- as a consequence of flow directed pulmonary artery catheterization. N Engl
rac Cardiovasc Surg 82:1, 1981. J Med 311:1152, 1984.
109. Shah KB, Rao TL, Laughlin S, et al: A review of pulmonary artery catheter- 134. Ford SE, Manley PN: Indwelling cardiac catheters: an autopsy study of
ization in 6245 patients. Anesthesiology 61:271, 1984. associated endocardial lesions. Arch Pathol Lab Med 106:314, 1982.
110. Fraser RS: Catheter-induced pulmonary artery perforation: pathologic and 135. Prochan H, Dittel M, Jobst C, et al: Bacterial contamination of pulmonary
pathogenic features. Hum Pathol 18:1246, 1987. artery catheters. Intensive Care Med 4:79, 1978.
111. Declen JD, Friloux LA, Renner JW: Pulmonary artery false-aneurysms sec- 136. Pinella JC, Ross DF, Martin T, et al: Study of the incidence of intravascular
ondary to Swan-Ganz pulmonary artery catheters. AJR Am J Roentgenol catheter infection and associated septicemia in critically ill patients. Crit
149:901, 1987. Care Med 11:21, 1983.
112. Thoms R, Siproudhis L, Laurent JF, et al: Massive hemoptysis from iatro- 137. Michel L, Marsh HM, McMichan JC, et al: Infection of pulmonary artery
genic balloon catheter rupture of pulmonary artery: successful early man- catheters in critically ill patients. JAMA 245:1032, 1981.
agement by balloon tamponade. Crit Care Med 15:272, 1987. 138. Greene JF, Fitzwater JE, Clemmer TP: Septic endocarditis and indwelling
113. Slacken A: Complications of invasive hemodynamic monitoring in the in- pulmonary artery catheters. JAMA 233:891, 1975.
tensive care unit. Curr Probl Surg 25:69, 1988. 139. Myers ML, Austin TW, Sibbald WJ: Pulmonary artery catheter infections:
114. Scuderi PE, Prough DS, Price JD, et al: Cessation of pulmonary artery a prospective study. Ann Surg 201:237, 1985.
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PEEP. Anesth Analg 62:236, 1983. Curr Infect Dis Rep 7:413, 2005.
115. Pace NL, Horton W: Indwelling pulmonary artery catheters: their relation- 141. Chatzinikolaou I, Hanna R, Darouiche R, et al: Prospective study of the
ship to aseptic thrombotic endocardial vegetations. JAMA 233:893, 1975. value of quantitative culture of organisms from blood collected through cen-
116. Dye LE, Segall PH, Russell RO, et al: Deep venous thrombosis of the upper tral venous catheters in differentiating between contamination and blood-
extremity associated with use of the Swan-Ganz catheter. Chest 73:673, stream infection. J Clin Microbiol 44:1834, 2006.
1978. 142. Weinstein RA, Stamm WE, Kramer L: Pressure monitoring devices: over-
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Chest 76:647, 1979. catheters. Infect Surg 1984;853.
118. Chastre J, Cornud F, Bouchama A, et al: Thrombosis as a complication 144. Heard SO, Davis RF, Sherertz RJ, et al: Influence of sterile protective sleeves
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Med 306:278, 1982. 145. Cobb DK, High KP, Sawyer RG, et al: A controlled trial of scheduled re-
119. Laster JL, Nichols WK, Silver D: Thrombocytopenia associated with placement of central venous and pulmonary artery catheters. N Engl J Med
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antibodies. Arch Intern Med 149:2285, 1989. 146. Berry AJ, Geer RT, Marshall BE: Alteration of pulmonary blood flow by
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121. Geha DG, Davis NJ, Lappas DG: Persistent atrial arrhythmias associated 147. Schluger J, Green J, Giustra FX, et al: Complication with use of flow-
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122. Sprung CL, Jacobs JL, Caralis PV, et al: Ventricular arrhythmias during 148. Isner JM, Horton J, Ronan JAS: Systolic click from a Swan-Ganz catheter:
Swan-Ganz catheterization of the critically ill. Chest 79:413, 1981. phonoechocardiographic depiction of the underlying mechanism. Am J Car-
123. Sprung CL, Pozen PG, Rozanski JJ, et al: Advanced ventricular arrhythmias diol 42:1046, 1979.
during bedside pulmonary artery catheterization. Am J Med 72:203, 1982. 149. Lawson D, Kushkins LG: A complication of multipurpose pacing pul-
124. Iberti TJ, Benjamin E, Grupzi L, et al: Ventricular arrhythmias during pul- monary artery catheterization via the external jugular vein approach [let-
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1985. 150. McLellan BA, Jerman MR, French WJ, et al: Inadvertent Swan-Ganz
125. Sprung CL, Marical EH, Garcia AA, et al: Prophylactic use of lidocaine catheter placement in the left pericardiophrenic vein. Cathet Cardiovasc
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pulmonary artery catheters. Chest 85:296, 1984. ventricle into the aorta. Anesthesiology 70:1019, 1989.
127. Damen J: Ventricular arrhythmia during insertion and removal of pul- 152. Lazzam C, Sanborn TA, Christian F: Ventricular entrapment of a Swan-
monary artery catheters. Chest 88:190, 1985. Ganz catheter: a technique for nonsurgical removal. J Am Coll Cardiol
128. Morris D, Mulvihill D, Lew WY: Risk of developing complete heart block 13:1422, 1989.
during bedside pulmonary artery catheterization in patients with left bundle 153. Ginosar Y, Sprung CL: The SwanGanz catheter: twenty-five years of mon-
branch block. Arch Intern Med 147:2005, 1987. itoring. Crit Care Clin 12:771, 1996.
129. Lavie CJ, Gersh BJ: Pacing in left bundle branch block during Swan-Ganz 154. Wiedermann HP, Matthay MA, Matthay RA: Cardiovascular-pulmonary
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1987. 156. http://www.clinicaltrials.gov. Accessed January 23, 2011.
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64 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

CHAPTER 5 TEMPORARY CARDIAC


PACING
SETH T. DAHLBERG

Temporary cardiac pacing may be urgently required for the onds) are important in the successful conversion of atrial flutter
treatment of cardiac conduction and rhythm disturbances com- to sinus rhythm.
monly seen in patients treated in the intensive care unit (ICU). In some clinical situations, pacing termination of atrial flut-
Therefore, ICU personnel should be familiar with the indica- ter may be preferable to synchronized cardioversion, which
tions and techniques for initiating and maintaining temporary requires sedation with its attendant risks. Pacing termination
cardiac pacing as well as the possible complications of this pro- is the treatment of choice for atrial flutter in patients with epi-
cedure. Recommendations for training in the performance of cardial atrial wires in place after cardiac surgery. It may be
transvenous pacing have been published by a Task Force of preferred as the means to convert atrial flutter in patients on
the American College of Physicians, American Heart Associ- digoxin and those with sick sinus syndrome, as these groups
ation and American College of Cardiology [1]. Competence often demonstrate prolonged sinus pauses after DC cardiover-
in the performance of transvenous pacing also requires the op- sion.
erator to have training in central venous access (Chapter 2) and Temporary pacing may be required for the prevention of
hemodynamic monitoring (Chapters 4 and 26) [25]. paroxysmal polymorphic ventricular tachycardia in patients
with prolonged QT intervals (torsades de pointes), particularly
when secondary to drugs [9,10]. Temporary cardiac pacing is
INDICATIONS FOR TEMPORARY the treatment of choice to stabilize the patient while a type
I antiarrhythmic agent exacerbating ventricular irritability is
CARDIAC PACING metabolized. In this situation, the pacing rate is set to provide
a mild tachycardia. The effectiveness of cardiac pacing proba-
As outlined in Table 5.1, temporary pacing is indicated in the bly relates to decreasing the dispersion of refractoriness of the
diagnosis and management of a number of serious rhythm and ventricular myocardium (shortening the QT interval).
conduction disturbances. Temporary ventricular pacing may be successful in termi-
nating ventricular tachycardia. If ventricular tachycardia must
be terminated urgently, cardioversion is mandated (Chapter 6).
Bradyarrhythmias However, in less urgent situations, conversion of ventricular
tachycardia via rapid ventricular pacing may be useful. The
The most common indication for temporary pacing in the ICU success of this technique depends on the setting in which ven-
setting is a hemodynamically significant or symptomatic brad- tricular tachycardia occurs. Overdrive ventricular pacing is
yarrhythmia such as sinus bradycardia or high-grade atrioven- often effective in terminating monomorphic ventricular tachy-
tricular (AV) block. cardia in a patient with remote myocardial infarction or in
Sinus bradycardia and AV block are commonly seen the absence of heart disease. This technique is less effective
in patients with acute coronary syndromes, hyperkalemia, when ventricular tachycardia complicates acute myocardial in-
myxedema, or increased intracranial pressure. Infectious pro- farction or cardiomyopathy. Rapid ventricular pacing is most
cesses such as endocarditis or Lyme disease [6] may impair successful in terminating ventricular tachycardia when the ven-
AV conduction. Bradyarrhythmias also result from treatment tricle can be captured (asynchronous pacing for 5 to 10 beats
or intoxication with digitalis, antiarrhythmic, beta-blocker, or at a rate of 50 beats per minute greater than that of the under-
calcium channel blocker medications and may also result from lying tachycardia). Extreme caution is advised, as pacing may
exaggerated vasovagal reactions to ICU procedures such as suc- result in acceleration of ventricular tachycardia or degenera-
tioning of the tracheobronchial tree in the intubated patient. tion to ventricular fibrillation; a cardiac defibrillator should be
Bradycardia-dependent ventricular tachycardia may occur in immediately available at the bedside.
association with ischemic heart disease.

Tachyarrhythmias DIAGNOSIS OF RAPID


RHYTHMS
Temporary cardiac pacing is used less often for the preven-
tion and termination of supraventricular and ventricular tach- Temporary atrial pacing electrodes may be helpful for the di-
yarrhythmias. agnosis of tachyarrhythmias when the morphology of the P
Atrial pacing may be effective in terminating atrial flut- wave and its relation to the QRS complexes cannot be deter-
ter and paroxysmal nodal supraventricular tachycardia [7,8]. mined from the surface electrocardiogram (ECG) [1113]. A
Atrial pacing in the ICU setting is most frequently performed recording of the atrial electrogram is particularly helpful in a
when temporary epicardial electrodes have been placed during rapid, regular, narrow-complex tachycardia in which the dif-
cardiac surgery. A critical pacing rate (usually 125% to 135% ferential diagnosis includes atrial flutter with rapid ventricular
of the flutter rate) and pacing duration (usually about 10 sec- response, and AV nodal reentrant or other supraventricular
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Chapter 5: Temporary Cardiac Pacing 65

TA B L E 5 . 1
INDICATIONS FOR ACUTE (TEMPORARY) CARDIAC PACING

A. Conduction disturbances
1. Symptomatic persistent third-degree AV block with inferior myocardial infarction
2. Third-degree AV block, new bifascicular block (e.g., right bundle branch block and left
anterior hemiblock, left bundle branch block, first-degree AV block), or alternating left and
right bundle branch block complicating acute anterior myocardial infarction
3. Symptomatic idiopathic third-degree AV block, or high-degree AV block
B. Rate disturbances
1. Hemodynamically significant or symptomatic sinus bradycardia
2. Bradycardia-dependent ventricular tachycardia
3. AV dissociation with inadequate cardiac output
4. Polymorphic ventricular tachycardia with long QT interval (torsades de pointes)
5. Recurrent ventricular tachycardia unresponsive to medical therapy

AV, atrioventricular.

tachycardia. This technique may also assist in the diagnosis of


wide-complex tachycardias in which the differential diagnosis EQUIPMENT AVAILABLE FOR
includes supraventricular tachycardia with aberrant conduc- TEMPORARY PACING
tion, sinus tachycardia with bundle branch block, and ventric-
ular tachycardia. Several methods of temporary pacing are currently available for
To record an atrial ECG, the ECG limb leads are connected use in the ICU. Transvenous pacing of the right ventricle or right
in the standard fashion and a precordial lead (usually V1 ) is con- atrium with a pacing catheter or modified pulmonary artery
nected to the proximal electrode of the atrial pacing catheter or catheter is the most widely used technique; intraesophageal,
to an epicardial atrial electrode. A multichannel ECG rhythm transcutaneous, and epicardial pacing are also available.
strip is run at a rapid paper speed, simultaneously demonstrat-
ing surface ECG limb leads as well as the atrial electrogram
obtained via lead V1 . This rhythm strip should reveal the con- Transvenous Pacing Catheters
duction pattern between atria and ventricles as antegrade, si-
multaneous, retrograde, or dissociated. Some of the many transvenous pacing catheters available for
use in the critical care setting are illustrated in Figure 5.1. Pac-
ing catheters range in size from 4 Fr (1.2 mm) to 7 Fr (2.1
mm). In urgent situations, or where fluoroscopy is unavailable,
ACUTE MYOCARDIAL a flow-directed flexible balloon-tipped catheter (Fig. 5.1, top)
INFARCTION may be placed in the right ventricle using ECG guidance. After
gaining access to the central venous circulation, the catheter
Temporary pacing may be used therapeutically or prophylac- is passed into the vein and the balloon inflated. After advanc-
tically in acute myocardial infarction [14]. Recommendations ing the catheter into the right ventricle, the balloon can be
for temporary cardiac pacing have been provided by a Task deflated and the catheter tip advanced to the right ventricular
Force of the American College of Cardiology and the Ameri- apex. Although the balloon-tipped catheter may avoid the need
can Heart Association (Table 5.2) [15]. Bradyarrhythmias un- for fluoroscopy, placement may be ineffective in the setting of
responsive to medical treatment that result in hemodynamic low blood flow during cardiac arrest or in the presence of se-
compromise require urgent treatment. Patients with anterior in- vere tricuspid regurgitation. Stiff catheters (Fig. 5.1, middle) are
farction and bifascicular block or Mobitz type II second-degree easier to manipulate but require insertion under fluoroscopic
AV block, while hemodynamically stable, may require a tem- guidance.
porary pacemaker, as they are at risk for sudden development A flexible J-shaped catheter (Fig. 5.1, bottom), designed for
of complete heart block with an unstable escape rhythm. temporary atrial pacing, is also available [23]. This lead is po-
Prophylactic temporary cardiac pacing has aroused debate sitioned by hooking it in the right atrial appendage under
for the role it may play in complicated anterior wall myocardial fluoroscopic guidance, providing stable contact with the atrial
infarction [16]. Thrombolytic therapy or percutaneous coro- endocardium. Either the subclavian or internal jugular venous
nary intervention, when indicated, should take precedence over approach may be used.
placement of prophylactic cardiac pacing, as prophylactic pac- A multilumen pulmonary artery catheter is available with a
ing has not been shown to improve mortality. Transthoracic right ventricular lumen. Placement of a small (2.4 Fr) bipolar
(transcutaneous) cardiac pacing is safe and usually effective pacing lead through the right ventricular lumen allows intracar-
[1720] and would be a reasonable alternative to prophylactic diac pressure monitoring and pacing through a single catheter
transvenous cardiac pacing, particularly soon after the admin- [24]. Details on its use and insertion are described in Chapter 4.
istration of thrombolytic therapy.
When right ventricular involvement complicates inferior
myocardial infarction, cardiac output may be very sensitive Esophageal Electrode
to ventricular preload and AV synchrony. Therefore, AV se-
quential pacing is frequently the pacing modality of choice in An esophageal pill electrode allows atrial pacing and record-
patients with right ventricular infarction [21,22]. ing of atrial depolarizations without requiring central venous
P1: OSO/OVY

66
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TA B L E 5 . 2
ACC/AHA RECOMMENDATIONS FOR TREATMENT OF ATRIOVENTRICULAR AND INTRAVENTRICULAR CONDUCTION DISTURBANCES
DURING STEMI

AV conduction
First-degree AV block Mobitz I second-degree AV block Mobitz II second-degree AV block
Normal AMI Non-AMI AMI Non-AMI AMI Non-AMI
Intraventricular
conduction Action Class Action Class Action Class Action Class Action Class Action Class Action Class

Normal OB 1 OB 1 OB 1 OB 2B OB 2A OB 3 OB 3
A 3 A 3 A 3 A* 3 A 3 A 3 A 3
TC 3 TC 2B TC 2B TC 1 TC 1 TC 1 TC 1
TV 3 TV 3 TV 3 TV 3 TV 3 TV 2A TV 2A
Old or new OB 1 OB 2B OB 2B OB 2B OB 2B OB 3 OB 3
fascicular block A 3 A 3 A 3 A* 3 A 3 A 3 A 3
(LAFB or LPFB) TC 2B TC 1 TC 2A TC 1 TC 1 TC 1 TC 1
TV 3 TV 3 TV 3 TV 3 TV 3 TV 2A TV 2B
Old BBB OB 1 OB 3 OB 3 OB 3 OB 3 OB 3 OB 3
A 3 A 3 A 3 A* 3 A 3 A 3 A 3
TC 2B TC 1 TC 1 TC 1 TC 1 TC 1 TC 1
TV 3 TV 2B TV 2B TV 2B TV 2B TV 2A TV 2A
New BBB OB 3 OB 3 OB 3 OB 3 OB 3 OB 3 OB 3
A 3 A 3 A 3 A* 3 A 3 A 3 A 3
TC 1 TC 1 TC 1 TC 1 TC 1 TC 2B TC 2B
TV 2B TV 2A TV 2A TV 2A TV 2A TV 1 TV 1
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TC 1 TC 1 TC 1 TC 1 TC 1 TC 2B TC 2B
TV 2B TV 2A TV 2A TV 2A TV 2A TV 1 TV 1
Alternating left and OB 3 OB 3 OB 3 OB 3 OB 3 OB 3 OB 3
right BBB A 3 A 3 A 3 A* 3 A 3 A 3 A 3
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TC 2B TC 2B TC 2B TC 2B TC 2B TC 2B TC 2B
TV 1 TV 1 TV 1 TV 1 TV 1 TV 1 TV 1
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Notes: This table is designed to summarize the atrioventricular (column headings) and intraventricular (row headings) conduction disturbances that may occur during acute anterior or nonanterior
STEMI, the possible treatment options, and the indications for each possible therapeutic option.
LAFB, left anterior fascicular block; LPFB, left posterior fascicular block; RBBB, right bundle-branch block; BBB, bundle-branch block; OB, observe; A, atropine; TC, transcutaneous pacing; TV,
temporary transvenous pacing; STEMI, ST elevation myocardial infarction; AV, atrioventricular; and MI, myocardial infarction; AMI, anterior myocardial infarction; non-AMI, nonanterior
QC: OSO/OVY

myocardial infarction.
Action: There are four possible actions, or therapeutic options, listed and classified for each bradyarrhythmia or conduction problem:
1. Observe: continued ECG monitoring, no further action planned.
2. A and A*: Atropine administered at 0.6 to 1.0 mg IV every 5 minutes to up to 0.04 mg/kg. In general, because the increase in sinus rate with atropine is unpredictable, this is to be avoided unless
there is symptomatic bradycardia that will likely respond to a vagolytic agent, such as sinus bradycardia or Mobitz I, as denoted by the asterisk in the table.
3. TC: Application of transcutaneous pads and standby transcutaneous pacing with no further progression to transvenous pacing imminently planned.
T1: OSO

4. TV: Temporary transvenous pacing. It is assumed, but not specified in the table, that at the discretion of the clinician, transcutaneous pads will be applied and standby transcutaneous pacing will be
LWBK834-Irwin-v1.cls

in effect as the patient is transferred to the fluoroscopy unit for temporary transvenous pacing.
Class: Each possible therapeutic option is further classified according to ACC/AHA criteria as Class 1: indicated, Class 2A: probably indicated, 2B: possibly indicated, and Class 3: not indicated.
Level of Evidence: This table was developed from (1) published observational case reports and case series; (2) published summaries, not meta-analyses, of these data; and (3) expert opinion, largely
from the prereperfusion era. There are no published randomized trials comparing different strategies of managing conduction disturbances after STEMI. Thus, the level of evidence for the
recommendations in this table is C.
How to Use the Table:
Example: 54-year-old man is admitted with an anterior STEMI and a narrow QRS on admission. On day 1, he develops a right bundle-branch block (RBBB), with a PR interval of 0.28 seconds.
1. RBBB is an intraventricular conduction disturbance, so look at row New bundle-branch block.
2. Find the column for First-Degree AV Block.
3. Find the Action and Class cells at the convergence.
4. Note that Observe and Atropine are class 3, not indicated; transcutaneous pacing (TC) is class 1. Temporary transvenous pacing (TV) is class 2B.
From Antman EM, Anbe DT, Armstrong PW, et al: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarctionexecutive summary. A report of the American
College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial
infarction). J Am Coll Cardiol 44:671719, 2004, with permission. Copyright 2004 American College of Cardiology Foundation.

67
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68 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

during thrombolytic therapy for acute myocardial infarction


[1719,2628]. When continued pacing is needed, transvenous
pacing is preferable.

Epicardial Pacing
The placement of epicardial electrodes requires open thora-
cotomy. These electrodes are routinely placed electively during
cardiac surgical procedures for use during the postoperative pe-
riod [12,13]. Typically, both atrial and ventricular electrodes
are placed for use in diagnosis of postoperative atrial arrhyth-
mias and for AV pacing. Because ventricular capture is not
always reliable, in patients with underlying asystole or an un-
stable escape rhythm additional prophylactic transvenous pac-
ing should be considered.

Pulse Generators for Temporary Pacing


FIGURE 5.1. Cardiac pacing catheters. Several designs are available Newer temporary pulse generators are now capable of ventric-
for temporary pacing in the critical care unit. Top: Balloon-tipped, ular, atrial, and dual chamber sequential pacing with adjustable
flow-directed pacing wire. Middle: Standard 5 Fr pacing wire. Bottom:
Atrial J-shaped wire.
ventricular and atrial parameters that include pacing modes
(synchronous or asynchronous), rates, current outputs (mA),
sensing thresholds (mV), and AV pacing interval/delay (mil-
liseconds). Since these generators have atrial sensing/inhibiting
cannulation. As mentioned earlier, detecting atrial depolariza- capability, they are also set with an upper rate limit (to avoid
tion aids in the diagnosis of tachyarrhythmias. Esophageal rapid ventricular pacing while tracking an atrial tachycar-
pacing has also been used to terminate supraventricular tachy- dia); in addition, an atrial pacing refractory period may be
cardia and atrial flutter [25]. Because the electrode can be un- programmed (to avoid pacemaker-mediated/endless-loop tach-
comfortable and may not give consistent, stable capture, the yarrhythmias).
esophageal electrode is typically limited to short-term use for Earlier dual chamber pulse generators may be limited to
diagnosis of arrhythmias in pediatric patients. sensing only ventricular depolarization (DVI mode). Without
atrial sensing, if the intrinsic atrial rate exceeds the atrial pacing
rate, the atrial pacing stimulus will fail to capture and AV se-
Transcutaneous External Pacemakers quential pacing will be lost with AV dissociation. Consequently,
with these models, the pacing rate must be set continuously
Transcutaneous external pacemakers have external patch elec- to exceed the intrinsic atrial rate to maintain AV sequential
trodes that deliver a higher current (up to 200 mA) and longer pacing.
pulse duration (20 to 40 milliseconds) than transvenous pace-
makers. External pacing can be implemented immediately and
the risks of central venous access avoided. Some patients may CHOICE OF PACING MODE
require sedation for the discomfort of skeletal muscle stimu-
lation from the high cutaneous current. Transcutaneous exter- A pacing mode must be selected when temporary cardiac pac-
nal pacemakers have been used to treat brady-asystolic cardiac ing is initiated. Common modes for cardiac pacing are out-
arrest, symptomatic bradyarrhythmias, and overdrive pacing lined in Table 5.3. The mode most likely to provide the great-
of tachyarrhythmias and prophylactically for conduction ab- est hemodynamic benefit should be selected. In patients with
normalities during myocardial infarction. They may be par- hemodynamic instability, establishing ventricular pacing is of
ticularly useful when transvenous pacing is unavailable, as paramount importance prior to attempts at AV sequential
in the prehospital setting, or relatively contraindicated, as pacing.

TA B L E 5 . 3
COMMON PACEMAKER MODES FOR TEMPORARY CARDIAC PACING

AOO Atrial pacing: pacing is asynchronous


AAI Atrial pacing, atrial sensing: pacing is on demand to provide a minimum
programmed atrial rate
VOO Ventricular pacing: pacing is asynchronous
VVI Ventricular pacing, ventricular sensing: pacing is on demand to provide a
minimum programmed ventricular rate
DVI Dual-chamber pacing, ventricular sensing: atrial pacing is asynchronous,
ventricular pacing is on demand following a programmed AV delay
DDD Dual-chamber pacing and sensing: atrial and ventricular pacing is on demand to
provide a minimum rate, ventricular pacing follows a programmed AV delay, and
upper-rate pacing limit should be programmed
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Chapter 5: Temporary Cardiac Pacing 69

Ventricular pacing effectively counteracts bradycardia and the recorded intracardiac electrogram. When the tip of the
is most frequently used in ICU patients; however, it cannot catheter reaches the right ventricle, the balloon is deflated and
restore normal cardiac hemodynamics because it disrupts AV the catheter advanced to the right ventricular apex. ST segment
synchrony [2931]. In patients with noncompliant ventricles elevation of the intracardiac electrogram due to a current of in-
(ischemic heart disease, left ventricular hypertrophy, aortic jury indicates contact of the catheter tip with the ventricular
stenosis, and right ventricular infarction), loss of the atrial con- endocardium.
tribution to ventricular stroke volume (the atrial kick) during After the tip of the pacing catheter is satisfactorily inserted
ventricular pacing may result in increased atrial pressure, inter- in the right ventricular apex, the leads are connected to the
mittent mitral and tricuspid regurgitation with reduced cardiac ventricular output connectors of the pulse generator, with the
output and blood pressure. pacemaker box in the off position. The pacemaker is then set
In addition to the hemodynamic benefit of atrial or AV se- to asynchronous mode (VOO) and the ventricular rate set to
quential pacing, the risk of atrial fibrillation or flutter may be exceed the patients intrinsic ventricular rate by 10 to 20 beats
reduced because of decreased atrial size and/or atrial pressure per minute. The threshold current for ventricular pacing is set
[32,33]. This suggests that patients with intermittent atrial fib- at 5 to 10 mA. Then the pacemaker is switched on. Satisfac-
rillation may be better maintained in normal sinus rhythm with tory ventricular pacing is evidenced by a wide QRS complex,
atrial or AV sequential pacing, rather than ventricular demand with ST segment depression and T wave inversion immediately
pacing. preceded by a pacemaker depolarization (spike). With pacing
from the apex of the right ventricle, the paced rhythm usu-
ally demonstrates a pattern of left bundle branch block on the
surface ECG [35].
PROCEDURE TO ESTABLISH Ventricular pacing is maintained as the output current for
TEMPORARY PACING ventricular pacing is slowly reduced. The pacing threshold is
defined as the lowest current at which consistent ventricular
After achieving venous access, most often via the internal jugu- capture occurs. With the ventricular electrode appropriately
lar or subclavian approach (Chapter 2), the pacing catheter is positioned at or near the apex of the right ventricle, a pacing
advanced to the central venous circulation and then positioned threshold of less than 0.5 to 1.0 mA should be achieved. If
in the right heart using fluoroscopic or ECG guidance [34]. the output current for continuous ventricular pacing is consis-
To position the electrode using ECG guidance, the patient is tently greater than 1 to 1.5 mA, the pacing threshold is too high.
connected to the limb leads of the ECG machine, and the dis- Possible causes of a high pacing threshold include relatively re-
tal (negative) electrode of the balloon-tipped pacing catheter is fractory endomyocardial tissue (fibrosis) or, most commonly,
connected to lead V1 with an alligator clip or a special adap- unsatisfactory positioning of the pacing electrode. The tip of
tor supplied with the lead. Lead V1 is then used to continu- the pacing electrode should be repositioned in the region of the
ously monitor a unipolar intracardiac electrogram. The mor- ventricular apex until satisfactory ventricular capture at a cur-
phology of the recorded electrogram indicates the position of rent of less than 1.0 mA is consistently maintained. After the
the catheter tip (Fig. 5.2). The balloon is inflated in the supe- threshold current for ventricular pacing has been established at
rior vena cava, and the catheter is advanced while observing a satisfactory level, the ventricular output is set to exceed the
threshold current at least threefold. This guarantees uninter-
rupted ventricular capture despite any modest increase in the
pacing threshold.
The pacemaker is now in VOO mode. However, the pacing
generator generally should be set in the VVI (demand) mode,
as this prevents pacemaker discharge soon after an intrinsic
or spontaneous premature depolarization, while the heart lies
in the electrically vulnerable period for induction of sustained
ventricular arrhythmias [36]. To set the pacemaker in VVI
mode, the pacing rate is set at 10 beats per minute less than the
intrinsic rate and the sensitivity control is moved from asyn-
chronous to the minimum sensitivity level. The sensitivity is
gradually increased until pacing spikes appear. This level is the
sensing threshold. The sensitivity is then set at a level slightly
below the determined threshold and the pacing rate reset to the
minimum desired ventricular rate.
If AV sequential pacing is desired, the atrial J-shaped pacing
catheter should be advanced into the right atrium and rotated
anteromedially to achieve a stable position in the right atrial
appendage; however, positioning the atrial catheter usually re-
quires fluoroscopy [34,37]. The leads are then connected to the
atrial output of the pulse generator. The atrial current is set to
20 mA and the atrial pacing rate adjusted to at least 10 beats
per minute greater than the intrinsic atrial rate. The AV in-
terval is adjusted at 100 to 200 milliseconds (shorter intervals
usually provide better hemodynamics), and the surface ECG is
inspected for evidence of atrial pacing (electrode depolarization
and capture of the atrium at the pacing rate).
FIGURE 5.2. Pattern of recorded electrogram at various locations in
the venous circulation. (From Harthorne JW, McDermott J, Poulin Atrial capture on ECG is indicated by atrial depolarization
FK: Cardiac pacing, in Johnson RA, Haber E, Austen WG (eds): The (P waves) immediately following the atrial pacing spikes. In pa-
Practice of Cardiology: The Medical and Surgical Cardiac Units at the tients with intact AV conduction, satisfactory atrial capture can
Massachusetts General Hospital. Boston, Little, Brown, 1980, with be verified by shutting off the ventricular portion of the pace-
permission.) maker and demonstrating AV synchrony during atrial pacing.
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70 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

As long as the atrial pacing rate continually exceeds the intrin- cannulation of the right internal jugular vein provided the sim-
sic sinus rate, the atrial P wave activity should track with the plest, most direct route to the right-sided cardiac chambers
atrial pacing spike. [41].
The dual-chamber temporary pacemaker may not have Complications of internal jugular venous cannulation may
atrial sensing capability. If not, the pacemaker will function in include pneumothorax, carotid arterial injury, venous throm-
a DVI mode (Table 5.3). Should the intrinsic atrial rate equal or bosis, and pulmonary embolism (Chapter 2) [42]. These risks
exceed the atrial pacing rate, the atrial stimulus will fail to cap- are minimized by knowledge of anatomic landmarks, adher-
ture and AV sequential pacing will be lost. If the pacemaker has ence to proved techniques, use of a small-caliber needle to lo-
atrial sensing capability, the atrial sensing threshold should be calize the vein before insertion of the large-caliber needle and
determined and an appropriate level set. The pacer will then use of ultrasound assistance (for full discussion see Chapter 2).
function in the DDD mode. The DDD mode is usually pre- Full-dose systemic anticoagulation, thrombolytic therapy, and
ferred, as it provides optimum cardiac hemodynamics through prior neck surgical procedures are relative contraindications to
a range of intrinsic atrial rates. In this mode, an upper-rate limit routine internal jugular vein cannulation [43].
must be set to prevent rapid ventricular pacing in response to Percutaneous subclavian venipuncture is also frequently
a paroxysmal supraventricular tachycardia. used for insertion of temporary pacemakers [36,44]. This ap-
proach should be avoided in patients with severe obstructive
lung disease or a bleeding diathesis (including thrombolytic
therapy), in whom the risk of pneumothorax or bleeding is
COMPLICATIONS OF increased.
TEMPORARY PACING Although insertion of a pacing lead via the brachial vein may
reduce the risk of central arterial injury or hematoma formation
Transvenous pacing in the ICU setting is most often performed in the patient receiving thrombolytic therapy or full-dose an-
via the internal jugular or subclavian approach. Appropriate ticoagulation, motion of the patients arm relative to the torso
selection of the optimal route requires an understanding of the may result in an unstable position of the pacing electrode [41].
results and complications of each technique [38,39]. The risk of infection may also be increased with this approach.
Complications of temporary pacing from any venous ac- The femoral venous approach is used for electrophysiologic
cess route include pericardial friction rub, arrhythmia, right studies or during cardiac catheterization when the catheter is
ventricular perforation, cardiac tamponade, infection, uninten- left in place for only a few hours. This approach is less de-
tional arterial injury, diaphragmatic stimulation, phlebitis, and sirable when long-term cardiac pacing is required, since there
pneumothorax. Using predominantly the subclavian or inter- is a risk of deep venous thrombosis or infection around the
nal jugular approaches, Donovan and Lee reported a 7% rate catheter approach [45]. Central venous access by the subcla-
of serious complications related to temporary cardiac pacing vian or internal jugular route provides more stable long-term
[40]. The Mayo Clinic experience revealed that percutaneous positioning of the pacing lead.

References
1. Francis GS, Williams SV, Achord JL, et al: Clinical competence in insertion of Association Task Force on Practice Guidelines (Writing Committee to revise
a temporary transvenous ventricular pacemaker: a statement for physicians the 1999 guidelines for the management of patients with acute myocardial
from the ACP/ACC/AHA Task Force on Clinical Privileges in Cardiology. infarction). J Am Coll Cardiol 44:671719, 2004.
Circulation 89:19131916, 1994. 16. Lamas GA, Muller JE, Zoltan GT, et al: A simplified method to predict oc-
2. Sankaranarayanan R, Msairi A, Davis G: Ten years on: has competence and currence of complete heart block during acute myocardial infarction. Am J
training in temporary transvenous cardiac pacing improved? Brit J Hosp Cardiol 57:1213, 1986.
Med 68:384387, 2007. 17. Falk RH, Ngai STA: External cardiac pacing: Influence of electrode place-
3. Birkhahn RH, Gaeta TJ, Tloczkowski J, et al: Emergency medicine-trained ment on pacing threshold. Crit Care Med 14:931, 1986.
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Emerg Med 43:469474, 2004. transcutaneous cardiac pacing. Circulation 76:1337, 1987.
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sustainable resource or training liability? QJM: Int J Med 96:783785, 2003. with the zoll noninvasive temporary pacemaker. Am Heart J 116:7, 1988.
5. Murphy JJ, Frain JP, Stephenson CJ: Training and supervision of temporary 20. Dunn DL, Gregory JJ: Noninvasive temporary pacing: experience in a com-
transvenous pacemaker insertion. Br J Clin Pract 49:126128, 1995. munity hospital. Heart Lung 1:23, 1989.
6. McAlister HF, Klementowicz PT, Andrews C, et al: Lyme carditis: an impor- 21. Love JC, Haffajee CI, Gore JM, et al: Reversibility of hypotension and shock
tant cause of reversible heart block. Ann Intern Med 110:339345, 1989. by atrial or atrioventricular sequential pacing in patients with right ventric-
7. Deo R, Berger R: The clinical utility of entrainment pacing. J Cardiovasc ular infarction. Am Heart J 108:5, 1984.
Electrophysiol 20:466470, 2009. 22. Topol EJ, Goldschlager N, Ports TA, et al: Hemodynamic benefit of atrial
8. Aronow WS: Treatment of atrial fibrillation and atrial flutter: Part II. Cardiol pacing in right ventricular myocardial infarction. Ann Intern Med 96:594,
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9. Khan IA: Long QT syndrome: diagnosis and management. Am Heart J 23. Littleford PO, Curry RC Jr, Schwartz KM, et al: Clinical evaluation of a
143:714, 2002. new temporary atrial pacing catheter: Results in 100 patients. Am Heart J
10. Passman R, Kadish A: Polymorphic ventricular tachycardia, long Q-T syn- 107:237, 1984.
drome, and torsades de pointes. Med Clin North Am 85:321341, 2001. 24. Simoons ML, Demey HE, Bossaert LL, et al: The Paceport catheter: a new
11. Waldo AL: Cardiac arrhythmias: their mechanisms, diagnosis, and manage- pacemaker system introduced through a Swan-Ganz catheter. Cathet Car-
ment. Philadelphia, PA, J.B. Lippincott, 1987. diovasc Diagn 15:66, 1988.
12. Reade MC: Temporary epicardial pacing after cardiac surgery: a practical 25. Benson DW. Transesophageal electrocardiography and cardiac pacing: the
review: part 1: general considerations in the management of epicardial pac- state of the art. Circulation 75:86, 1987.
ing [erratum appears in Anaesthesia 62(6):644, 2007]. [Review] [26 refs]. 26. Luck JC, Grubb BP, Artman SE, et al: Termination of sustained ventric-
Anaesthesia 62:264271, 2007. ular tachycardia by external noninvasive pacing. Am J Cardiol 61:574,
13. Reade MC: Temporary epicardial pacing after cardiac surgery: a practical 1988.
review. Part 2: Selection of epicardial pacing modes and troubleshooting. 27. Kelly JS, Royster RL, Angert KC, et al: Efficacy of noninvasive transcuta-
Anaesthesia 62:364373, 2007. neous cardiac pacing in patients undergoing cardiac surgery. Anesthesiology
14. Brady WJ Jr, Harrigan RA: Diagnosis and management of bradycardia and 70:747, 1989.
atrioventricular block associated with acute coronary ischemia. Emerg Med 28. Blocka JJ: External transcutaneous pacemakers. Ann Emerg Med 18:1280,
Clin North Am 19:371384, xixii, 2001. 1989.
15. Antman EM, Anbe DT, Armstrong PW, et al: ACC/AHA guidelines for the 29. Romero LR, Haffajee CI, Doherty P, et al: Comparison of ventricular func-
management of patients with ST-elevation myocardial infarctionexecutive tion and volume with A-V sequential and ventricular pacing. Chest 80:346,
summary. A report of the American College of Cardiology/American Heart 1981.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 6: Cardioversion and Defibrillation 71

30. Knuse I, Arnman K, Conradson TB, et al: A comparison of the acute and long- 37. Holmes DR Jr: Temporary cardiac pacing, in Furman S, Hayes DL, Holmes
term hemodynamic effects of ventricular inhibited and atrial synchronous DR, Jr (eds): A Practice of Cardiac Pacing. Mount Kisco, NY, Futura, 1989.
ventricular inhibited pacing. Circulation 65:846, 1982. 38. Murphy JJ: Current practice and complications of temporary transvenous
31. Murphy P, Morton P, Murtaugh G, et al: Hemodynamic effects of different cardiac pacing. BMJ 312:1134, 1996.
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acute myocardial infarction. Pacing Clin Electrophysiol 15:1396, 1992. maker insertion. Br J Hosp Med 53:155161, 1995.
32. Neto VA, Costa R, Da Silva KR, et al: Temporary atrial pacing in the preven- 40. Donovan KD, Lee KY: Indications for and complications of temporary
tion of postoperative atrial fibrillation. Pacing Clin Electrophysiol 30[Suppl transvenous cardiac pacing. Anaesth Intensive Care 13:63, 1984.
1]:S79S83, 2007. 41. Hynes JK, Holmes DR, Harrison CE: Five year experience with temporary
33. Levy T, Fotopoulos G, Walker S, et al: Randomized controlled study inves- pacemaker therapy in the coronary care unit. Mayo Clin Proc 58:122, 1983.
tigating the effect of biatrial pacing in prevention of atrial fibrillation after 42. Chastre J, Cornud F, Bouchama A, et al: Thrombosis as a complication of
coronary artery bypass grafting. Circulation 102:13821387, 2000. pulmonary-artery catheterization via the internal jugular vein: Prospective
34. Harthorne JW, McDermott J, Poulin FK: Cardiac pacing, in Johnson RA, evaluation by phlebography. N Engl J Med 306:278, 1982.
Haber E, Austen WG (eds): The Practice of Cardiology: The Medical and 43. Austin JL, Preis LK, Crampton RS, et al: Analysis of pacemaker malfunc-
Surgical Cardiac Units at the Massachusetts General Hospital. Boston, Little, tion and complications of temporary pacing in the coronary care unit. Am J
Brown, 1980. Cardiol 49:301, 1982.
35. Morelli RL, Goldschlager N: Temporary transvenous pacing: resolving 44. Linos DA, Mucha P Jr, van Heerden JA: Subclavian vein: a golden route.
postinsertion problems. J Crit Illness 2:73, 1987. Mayo Clin Proc 55:315, 1980.
36. Donovan KD: Cardiac pacing in intensive care. Anaesth Intensive Care 45. Nolewajka AJ, Goddard MD, Brown TC: Temporary transvenous pacing
13:41, 1984. and femoral vein thrombosis. Circulation 62:646, 1980.

CHAPTER 6 CARDIOVERSION AND


DEFIBRILLATION
MARK S. LINK AND NAOMI F. BOTKIN

The use of electric shock to terminate arrhythmia is one of arrhythmias by simultaneously depolarizing all excitable tissue,
the critical findings of the last century and underlies much disrupting the process of reentry.
of the modern treatment of arrhythmias. Thanks to the pi- Arrhythmias may also be due to disorders of impulse for-
oneering work of Zoll et al. [1] and Lown et al. [2] in the mation (increased automaticity or triggered activity). These in-
second half of the twentieth century, the use of electric shock clude sinus tachycardia, focal atrial tachycardia, and idiopathic
gained widespread acceptance. Although incorporating the ventricular tachycardias. Sinus tachycardia is a physiologic re-
same mechanism and physics, Cardioversion refers to the use sponse and not a pathologic tachycardia; thus, sinus tachycar-
of direct-current electric shock to terminate arrhythmias other dia will not respond to cardioversion, but atrial tachycardias
than ventricular fibrillation, while Defibrillation refers to the and ventricular tachycardias generally will terminate.
termination of ventricular fibrillation. Cardioversion shocks Insight into the effect of shock on fibrillating myocardial
are synchronized to the QRS to avoid the initiation of ventric- cells has grown in the past few decades. Although it was ini-
ular fibrillation which may result from shocks on the T-wave tially thought that all activation fronts had to be terminated
while defibrillation occurs with unsynchronized shocks. simultaneously to stop atrial and ventricular fibrillation [4],
it is now believed that if the vast majority of myocardium is
silenced, the remaining mass is insufficient to perpetuate the ar-
rhythmia [5]. The effect of shock on fibrillating myocardium is
PHYSIOLOGY OF ARRHYTHMIA complex and is dependent on multiple factors including energy,
AND SHOCK waveform, and myocardial refractory state [6]. Electric shocks
at low energy levels may fail to terminate atrial and ventricular
Arrhythmias may be due to reentry, increased automaticity, or fibrillation [7]. Atrial and ventricular arrhythmias may also be
triggered activity. Reentry refers to the phenomenon in which a terminated by the shock and then reinitiated shortly thereafter.
wave of excitation travels repeatedly over a closed pathway or And finally, ventricular fibrillation can be triggered in patients
circuit of conduction tissue. Reentry requires slow conduction not already in this rhythm if shock occurs on the vulnerable
in a portion of myocardium so that by the time the impulse exits portion of the T wave. Thus, synchronization of shocks with
the slowly conducting portion the remaining myocardium has the R wave will minimize the risk.
repolarized and is hence able to be depolarized again.
Many of the commonly encountered arrhythmias are due
to a fixed reentrant mechanism, including atrial flutter, atri-
oventricular (AV) nodal reentrant tachycardia (AVNRT), AV INDICATIONS AND
reentrant tachycardia (AVRT), and most ventricular tachycar- CONTRAINDICATIONS
dias. Atrial fibrillation, once thought exclusively reentrant, has
been shown to be caused by foci in the pulmonary veins in Cardioversion and defibrillation are performed for a variety
many individuals [3]. Atrial fibrillation may also be secondary of reasons in the intensive care setting. In the case of hemody-
to functional reentry. Ventricular fibrillation is also due to func- namic instability due to tachyarrhythmia of nearly any type, the
tional reentry. Cardioversion and defibrillation terminate these urgent use of shock is strongly indicated. One must be careful,
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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72 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

however, not to shock sinus tachycardia, which is commonly patient safety and comfort become paramount. As with any
present in patients who are hypotensive for noncardiac reasons. procedure, informed consent should be obtained. Patients
Acute congestive heart failure and angina that are secondary to should refrain from eating and drinking for several hours to de-
an acute tachyarrhythmia are also indications for urgent car- crease the risk of regurgitation and aspiration. Constant heart
dioversion; however, there is usually sufficient time to provide rhythm monitoring should be used throughout the procedure
some sedation. Care must be taken not to shock tachycardias and a 12-lead electrocardiogram should be obtained before and
that are secondary to the heart failure or chest pain. In the after the shock.
absence of hemodynamic instability or significant symptoms, Medications with rapid onset and short half-life are favored
cardioversion is usually considered elective and the risks and for achieving analgesia, sedation, and amnesia. The combina-
benefits of the procedure must be carefully weighed. tion of a benzodiazepine, such as midazolam, and a narcotic,
Extreme caution should be exercised in patients with dig- such as fentanyl, is a common choice in the absence of anesthe-
italis toxicity or electrolyte imbalance because of the in- siology assistance. Propofol is often used when an anesthesiol-
creased risk of ventricular tachycardia or fibrillation after being ogist is present to assist with airway management and sedation.
shocked. Patients with severe sinus node disease may exhibit Existing hospital policies for monitoring during moderate se-
significant bradyarrhythmia after cardioversion from atrial fib- dation should be followed, including frequent assessment of
rillation. In addition, patients who have been in atrial fibrilla- blood pressure and pulse oximetry. Supplemental oxygen is
tion for greater than 48 hours are at risk for thromboembolism delivered via nasal cannula or face mask.
after cardioversion; appropriate measures should be taken to
minimize this risk (see later). Shock Waveforms
Defibrillators that employ biphasic waveforms have largely
CLINICAL COMPETENCE replaced those using monophasic waveforms. Advantages of
biphasic waveforms are lower defibrillation thresholds, mean-
A clinical competence statement by the American College of ing shocks using biphasic waveforms require less energy to
Cardiology and American Heart Association outlines the cog- achieve defibrillation [6], and they are less likely to cause skin
nitive and technical skills required for the successful and safe burns and myocardial damage. Both biphasic truncated expo-
performance of elective external cardioversion (Table 6.1). A nential waveform and biphasic rectilinear waveform are com-
minimum of eight cardioversions should be supervised before a mercially available, with the former being more common. Ran-
physician is considered competent to perform the procedure in- domized trials comparing the two types of biphasic waveforms
dependently. In addition, a minimum of four procedures should in the cardioversion of atrial fibrillation have failed to show
be performed annually to maintain competence [8]. any significant difference in efficacy [911].
The efficacy of biphasic shocks in the termination of ven-
tricular fibrillation has been well established [12,13]. Further-
Methods more, clinical studies of atrial fibrillation cardioversion have
established the superiority of biphasic over monophasic wave-
form shocks [14,15]. For instance, one study demonstrated the
Patient Preparation equivalent efficacy of a 120 to 200 J biphasic sequence with a
In the case of unconsciousness due to tachyarrhythmia, the 200 to 360 J monophasic sequence [15]. Biphasic waveforms
shock must be performed urgently. In more elective settings, allow fewer shocks to be given and a lower total energy delivery

TA B L E 6 . 1
COGNITIVE AND TECHNICAL SKILLS NECESSARY FOR PERFORMING EXTERNAL CARDIOVERSION

Physicians should have knowledge of the following:


Electrophysiologic principles of cardioversion
Indications for the procedure
Anticoagulation management
Proper use of antiarrhythmic therapy
Use of sedation and the management of overdose
Direct current cardioversion equipment, including the selection of appropriate energy and synchronization.
Treatment of possible complications, including advanced cardiac life support (ACLS), defibrillation, and pacing
Proper placement of paddles or pads
Appropriate monitor display and recognition of arrhythmias
Ability to differentiate failure to convert atrial fibrillation from an immediate recurrence of atrial fibrillation
Baseline 12-lead electrocardiogram reading, recognition of acute changes, drug toxicity, and contraindications
Physicians should have the following technical skills:
Proper preparation of skin and electrode placement, including application of saline jelly or saline soaked gauze
Achievement of artifact-free monitored strips and synchronization signal/marker
Technically acceptable 12-lead electrocardiograms before and after cardioversion
Temporary pacing and defibrillation capabilities
Ability to perform advanced cardiac life support, including proper airway management

From Tracy CM, Akhtar M, DiMarco JP, et al: American College of Cardiology/American Heart Association 2006 Update of the Clinical Competence
Statement on invasive electrophysiology studies, catheter ablation, and cardioversion: A report of the American College of Cardiology/American Heart
Association/American College of Physicians-American Society of Internal Medicine Task Force on Clinical Competence. Circulation 114:16541668,
2006.
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Chapter 6: Cardioversion and Defibrillation 73

A B
B

FIGURE 6.1. A: Self-adhesive defibrillator pads in the anterior and lateral positions. B: Self-adhesive
defibrillator pad in the posterior position. When posterior positioning is used, the second pad is placed
anteriorly.

[14]. Whether or not this translates into a significant clinical Using the Defibrillator
advantage remains to be demonstrated. However, there is ev-
External defibrillators are designed for easy operation. After
idence that biphasic shocks result in less dermal injury [14].
the patient is adequately prepared and the electrodes are ap-
Although an animal model suggested better maintenance of
plied, attention may be turned to the device itself. If the QRS
cardiac function after biphasic shocks [16], human data on
amplitude on the rhythm tracing is small and difficult to see,
myocardial function are unavailable.
a different lead should be selected. If cardioversionrather
than defibrillationis to be performed, the synchronization
function should be selected. Many defibrillators require that
Electrodes external leads be applied for synchronization. The appropri-
Until recently, hand-held paddles were the only available means ate initial energy is selected. Finally, the capacitor is charged,
of cardioversion or defibrillation. Self-adhesive pads have be- the area is cleared, and the shock is delivered. One should
come more common in the past few years, although paddles be aware that the synchronization function is automatically de-
may still be used. Limited data are available comparing the selected after each shock in most devices, meaning that it must
two modalities, but one study suggested the superiority of pad- be manually reselected prior to any further shock delivery if
dles over pads in cardioverting atrial fibrillation [17]). This another synchronized shock is desired.
phenomenon might be explained by the lower transthoracic Table 6.2 provides a checklist for physicians involved in
impedance achieved with paddles [18]. Whichever modality cardioversion. Table 6.3 gives recommendations for the initial
is used, impedance can be minimized by avoiding positioning energy selection for defibrillation and cardioversion of vari-
over breast tissue, by clipping body hair when it is excessive ous arrhythmias. Recommendations specific to each device are
[19], by delivering the shock during expiration, and by firm available in the manufacturers manuals and should be con-
pressure on the pads or paddles. sulted by physicians unfamiliar with their particular device.
The optimal anatomic placement of pads and paddles
is controversial; however, the general principal holds that
the heart must lie between the two electrodes [6]. Both TA B L E 6 . 2
anteriorlateral and anteriorposterior placements are accept-
able (Fig. 6.1). The anterior paddle is placed on the right CHECKLIST FOR PERFORMING CARDIOVERSION
infraclavicular chest. In anteriorlateral placement, the lat-
eral paddle should be located lateral to the left breast and Preparing the patient:
should have a longitudinal orientation, since this results in 1. Ensure NPO status
a lower transthoracic impedance than horizontal orientation 2. Obtain informed consent
[20]. When anteriorposterior positioning is used, the pos- 3. Apply self-adhesive pads (clip hair if needed)
terior pad is commonly located to the left of the spine at 4. Apply external lead
the level of the lower scapula, although some physicians fa- 5. Achieve adequate sedation and analgesia
vor placement to the right of, or directly over, the spine. 6. Monitor vital signs and cardiac rhythm throughout
There are data to suggest that anteriorposterior placement Performing the cardioversion:
is more successful in the cardioversion of atrial fibrillation 1. Select initial energy appropriate for specific device
than anteriorlateral positioning when monophasic wave- 2. Select the synchronization function
forms are used [21]. It is thought that anteriorposterior po- 3. Confirm that arrhythmia is still present
sitioning directs more of the delivered energy to the atria 4. Charge, clear, and deliver shock
than anteriorlateral placement. However, a study employing 5. If no change in rhythm, escalate energy as appropriate
biphasic waveforms failed to show any difference of success
with anteriorlateral compared with anteriorposterior pad NPO, nil per os.
positions [22].
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74 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 6 . 3
SUGGESTED INITIAL ENERGY FOR CARDIOVERSION AND DEFIBRILLATION

Rhythm Monophasic (J) Biphasic (J)

Ventricular fibrillation, pulseless ventricular tachycardia 360 120200


Ventricular tachycardia with pulse 100 100
Atrial fibrillation 200 100200
Atrial flutter 50100 50

ventricular tachycardia are treated with unsynchronized, high-


Treatment of Ventricular Fibrillation and energy shocks of 120 to 200 J with biphasic defibrillators (or
Pulseless Ventricular Tachycardia 360 J in the case of devices that use monophasic waveforms). If
there is any confusion regarding which energy should be used
The algorithm for the treatment of pulseless ventricular tachy- it is best to shock with the highest available energy.
cardia and ventricular fibrillation in the most recently pub-
lished American Heart Association guidelines contains some
important changes from the previous guidelines [23]. Rather Treatment of Wide Complex
than beginning with three sequential shocks, the guidelines rec- Tachycardia with a Pulse
ommend only one shock followed by five cycles of cardiopul-
monary resuscitation (CPR) before the rhythm is reassessed When a pulse is present, a regular, wide complex tachycar-
[6]. This change was prompted by new data demonstrating dia may be ventricular tachycardia, supraventricular tachy-
that a single biphasic shock was more efficacious than three cardia with aberrant conduction, or a supraventricular
monophasic shocks in termination of ventricular fibrillation. tachycardia with preexcitation. If signs of instability are present
In addition, three sequential shocks involve a substantial inter- (such as chest pressure, altered mental status, hypotension, or
ruption in CPR, which has been shown to be associated with a heart failure) and are thought to be secondary to the tachy-
decreased odds of survival [24]. In the 2010 algorithm, vaso- cardia, urgent cardioversion is indicated. A starting energy of
pressors (epinephrine or vasopressin) may be given before or af- 100 J is recommended when a monophasic shock waveform is
ter the second shock, and antiarrhythmics such as amiodarone being used. The optimal initial energy with biphasic devices is
and lidocaine may be considered before or after the second unknown but it would seem reasonable to begin at 100 J. The
shock (Table 6.4). Both ventricular fibrillation and pulseless energy should be escalated with each successive shock, such as
200, 300, and 360 J [25].
If the patient is stable, however, one might consider enlisting
the assistance of an expert in distinguishing between ventricu-
TA B L E 6 . 4 lar and supraventricular arrhythmia. If this is not possible, it is
TREATMENT OF VENTRICULAR FIBRILLATION AND generally safest to assume a ventricular etiology. Stable ventric-
PULSELESS VENTRICULAR TACHYCARDIA ular tachycardia may be treated initially with antiarrhythmic
agents such as amiodarone, lidocaine, or procainamide. Elec-
Assess airway, breathing, and circulation tive cardioversion can be performed if necessary, once sedation
Assess rhythm and analgesia are assured.
Deliver 1 shock Wide complex tachycardia that appears irregular is usually
Monophasic: 360 J atrial fibrillation with aberrant conduction but may also be
Biphasic: use device specific energy; if unknown, maximum polymorphic ventricular tachycardia or torsades de pointes. If
energy the arrhythmia is atrial fibrillation, treatment should follow
Resume compressions immediately and perform five cycles of the recommendations for atrial fibrillation (see later). How-
CPR ever, if the WolffParkinsonWhite Syndrome is suspected, AV
Check rhythmif still VT/VF, shock again nodal blocking agents are contraindicated and procainamide
Monophasic: 360 J or ibutilide should be used. If the patient is hypotensive or in
Biphasic: same as first shock or higher dose shock or if the rhythm is thought to be polymorphic ventricular
Resume compressions immediately and perform five cycles of tachycardia then an unsynchronized shock is advised.
CPR
Give a vasopressor during CPR, either before or after the second
shock Treatment of Supraventricular Tachycardia
Epinephrine 1 mg IV/IO, repeat every 35 min, OR
Vasopressin 40 U IV/IO may replace First or second dose of The most common narrow complex tachycardia is sinus
epinephrine tachycardia, which is an appropriate cardiac response to
Check rhythmif still VT/VF, shock again some other physiologic condition. Atrial fibrillation and atrial
Consider an antiarrhythmic before or after second shock: flutter are the next most common, followed by AVNRT,
Amiodarone 300 mg IV/IO once, then consider additional AV-reciprocating tachycardia (AVRT) and atrial tachycar-
150 mg once OR dia. Supraventricular tachycardiadefined as a nonventricular
Lidocaine 1 to 1.5 mg/kg first dose, then 0.5 to 0.75 mg/kg tachycardia other than sinus tachycardiashould be suspected
IV/IO, maximum three doses. when the arrhythmia starts suddenly, when it is more rapid than
maximal sinus rates (220-age), and when P waves are absent
IO, intraosseous; IV, intravenous; VF, ventricular fibrillation; or closely follow the QRS. Initial therapy involves vagal ma-
VT, ventricular tachycardia. neuvers and adenosine. If these fail, nondihydropyridine cal-
cium channel antagonists or beta-blockers may terminate the
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 6: Cardioversion and Defibrillation 75

arrhythmia. Cardioversion is indicated only rarely for clinical Dofetilide, flecainide, ibutilide, propafenone, amiodarone,
instability, usually in patients with underlying heart disease in and quinidine have been demonstrated to have some degree of
whom the initial therapies fail. efficacy in restoring sinus rhythm [27]. Each of these medica-
tions has potential toxicities including malignant arrhythmias
and hypotension. The risks and benefits should be carefully
Treatment of Atrial Fibrillation and Flutter weighed when selecting a pharmacologic agent. Although beta-
blockers and calcium channel antagonists are often believed to
facilitate cardioversion, their efficacy has not been established
Rate Control
in controlled trials.
Although the majority of patients with atrial fibrillation and
flutter remain hemodynamically stable, many develop bother- Management of Resistant Atrial Fibrillation
some symptoms such as palpitations, chest pressure, and, oc- Electrical cardioversion is unsuccessful in up to 10% of atrial
casionally, pulmonary edema. However, a rapid ventricular re- fibrillation and atrial flutter, most often because of early re-
sponse is usually secondary torather than the cause of heart currences of arrhythmia. The duration of atrial fibrillation is
failure and ischemia. Beta-blockers and nondihydropyridine inversely related to the probability of successful cardioversion.
calcium channel antagonists are used to slow the ventricular re- When cardioversion fails to even temporarily terminate the
sponse rate by slowing AV nodal conduction. Many patients be- arrhythmia, the operators technique should be reviewed and
come asymptomatic or minimally symptomatic with adequate modified. Electrode position may be altered, from anterior
rate control, allowing the decision about cardioversion to be posterior to anteriorlateral or vice versa. Firmer pressure may
made electively. be employed via the paddles or pads. If a device that deliv-
ers monophasic waveform shocks is being employed, it may be
Electrical Cardioversion exchanged for one that delivers biphasic waveform shocks. Ibu-
Cardioversion for atrial fibrillation or flutter is usually per- tilide may be initiated prior to another attempt at cardioversion
formed electively. The risk of thromboembolism dictates a [32]. Other antiarrhythmic agents may reduce the recurrence
thoughtful decision about treatment options. When cardiover- of arrhythmia.
sion is performed, an appropriate initial starting dose is 100
to 200 J for monophasic waveform shock and 120 to 200 J Complications of Defibrillation
for biphasic shock. Atrial flutter responds to lower energy, so a
starting dose of 50 to 100 J is recommended with a monopha- and Cardioversion
sic waveform. The ideal starting energy for biphasic devices
is unknown, so 50 to 100 J is reasonable. If atrial fibrillation Burns
or flutter fails to terminate, shock energy should be escalated. Shock can cause first-degree burns and pain at the paddle or
For most defibrillators, the synchronization function must be pad site. One study documented moderate to severe pain in
selected after each shock. nearly one quarter of patients undergoing cardioversion. Pain
was directly related to total energy delivered and number of
Anticoagulation shocks [33]. Another study showed a lower rate of dermal in-
Patients with atrial fibrillation or flutter may develop throm- jury with biphasic rather than monophasic shocks, probably
bus in the left atrial appendage or left atrial cavity, leading due to the lower energy necessary with biphasic shocks [14].
to thromboembolism during or after cardioversion. One study The lowest effective energy should be used to minimize skin
demonstrated a risk of pericardioversion thromboembolism of injury. In addition, saline-soaked gauzes between the skin and
5.3% in patients who were not anticoagulated and 0.8% in the paddles, rather than conductive gel, will minimize burns.
those who were [26].
Thromboembolism
There is general agreement that cardioversion of patients
who have been in atrial fibrillation for less than 24 to 48 hours Cardioversion of atrial fibrillation and atrial flutter carries a
is very unlikely to cause thromboembolism. Current guidelines risk of thromboembolism. Up to 7% of patients in atrial fib-
indicate that pericardioversion anticoagulation with heparin rillation who undergo cardioversion without receiving antico-
or low molecular weight heparin is optional in these patients agulation may experience this complication [26], and antico-
[27]. Individuals in atrial fibrillation or flutter for greater than agulation is standard of care for those in atrial fibrillation or
48 hours are at risk for thromboembolism. In these individu- flutter for those in arrhythmias more than 48 hours [27].
als, a transesophageal echocardiogram is necessary to exclude
left atrial thrombus in all but the most emergent cases [28,29]. Arrhythmia
Alternatively, one can therapeutically anticoagulate for at least Bradyarrhythmias such as sinus arrest and sinus bradycardia
3 weeks prior to cardioversion. Most physicians will anticoag- are common immediately after shock and are almost always
ulate for a few weeks after cardioversion, as the risk of throm- short lived. Patients who have atrial fibrillation may have con-
boembolism still exists during this period. comitant sinus node dysfunction that is masked by the atrial
fibrillation and unmasked by cardioversion.
Pharmacologic Cardioversion Ventricular tachycardia and ventricular fibrillation can oc-
Cardioversion can be achieved not only electrically but casionally be precipitated by shock, particularly in patients
also pharmacologically. Pharmacologic cardioversion is used with digitalis toxicity or hypokalemia [34,35]. Elective car-
mainly for atrial fibrillation and flutter of relatively short du- dioversion should therefore be avoided in patients with these
ration. Although electrical cardioversion is quicker and has conditions. If cardioversion or defibrillation must be performed
a higher probability of success, pharmacologic cardioversion urgently, one should anticipate the ventricular arrhythmias to
does not require sedation. The risk of thromboembolism with be more refractory to shock than usual.
pharmacologic cardioversion has not been well established but
is thought to be similar to that of electric shock because it is
Myocardial Damage
the return of sinus rhythm rather than the shock itself that is Occasionally, one may see transient ST segment elevations on
believed to precipitate thromboembolism [30,31]. postshock electrocardiograms [36]. This is unlikely to signify
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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76 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

myocardial injury. Although a study of cardioversion using external electric shock should never be placed over the device.
higher-than-usual energy levels demonstrated an increase in In addition, interrogation of the device immediately after any
creatine-kinaseMB levels above that expected from skeletal external shock delivery is recommended.
muscle damage in 10% of patients, there was no elevation in
troponin-T or -I seen [37]. This observation suggests that clin-
ically significant myocardial damage from cardioversion or de-
Chest Thump
fibrillation is unlikely. Nonetheless, it has been suggested that The use of a manual thump on the chest to successfully termi-
any two consecutive shocks be delivered no less than 1 minute nate ventricular tachycardia was described in several patients
apart to minimize the chance of myocardial damage [38]. Of in 1970 [39]. Unfortunately, this technique may inadvertently
course, this recommendation applies only to nonemergent sit- trigger ventricular fibrillation if the blow happens to fall dur-
uations. ing the vulnerable period of the ventricle [40]. A chest thump is
extremely unlikely to terminate ventricular fibrillation [41,42].
For these reasons, chest thump is considered a therapy of last
Miscellaneous Topics resort, administered only to a pulseless patient when a defib-
rillator is unavailable and unlikely to become available soon.
It should not be administered when a pulse is present unless a
Patients with Implanted Pacemakers and Defibrillators
defibrillator is immediately available.
Patients with implanted pacemakers and defibrillators may un-
dergo external cardioversion and defibrillation safely. How-
ever, one must be aware of the possibility that external energy
Cardioversion and Defibrillation in Pregnancy
delivery may alter the programming of the internal device. Fur- Cardioversion and defibrillation have been performed in all
thermore, energy may be conducted down an internal lead, trimesters of pregnancy without obvious adverse fetal effects
causing local myocardial injury and a resultant change in the or premature labor [43]. It has been suggested that the fetal
pacing or defibrillation threshold. The paddles or pads used for heart rhythm be monitored during cardioversion [44].

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Chapter 7: Pericardiocentesis 77

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CHAPTER 7 PERICARDIOCENTESIS
CRAIG S. SMITH AND RICHARD C. BECKER

Pericardiocentesis is a potentially life-saving procedure per- needle passage rates approaching 90% and relief of tamponade
formed in the critical care setting. In contrast to other cardiac in over 97% [7]. As a result, the 2004 European Society of Car-
conditions, however, there is a paucity of randomized clinical diology (ESC) recommends pericardiocentesis as the method
data to help guide physicians in the diagnosis and manage- of choice for pericardial fluid removal/sampling [8]. Surgical
ment of pericardial diseases. This chapter reviews the indica- intervention is recommended for recurring large effusions for
tions for emergent and urgent pericardiocentesis, summarizes which repeated pericardiocentesis has not been effective, loc-
the pathobiology of pericardial effusions, and provides a step- ulated or posterior effusions of hemodynamic consequence,
by-step approach to pericardiocentesis, including management purulent pericarditis, traumatic hemopericardium, constrictive
of patients following the procedure. pericarditis, and effusions due to aortic dissection [8]. When-
ever possible, elective pericardiocentesis should be performed
by an experienced operator using echocardiographic guidance.
While generally safe, it should be performed in a location with
INDICATIONS FOR adequate physiologic monitoring to assess any hemodynamic
PERICARDIOCENTESIS sequelae from complications and to aid in the diagnosis of
effusive-constrictive pericarditis.
The initial management of patients with a known or suspected In contrast to diagnostic pericardiocentesis, the manage-
pericardial effusion is largely determined by clinical status. In ment of hemodynamically compromised patients requires
the absence of hemodynamic instability or suspected purulent emergent removal of pericardial fluid to restore adequate ven-
bacterial pericarditis, there is no need for emergent or urgent tricular filling (preload) and hasten clinical stabilization. Ag-
pericardiocentesis. Diagnostic pericardiocentesis may be per- gressive fluid resuscitation and inotropic agents have been
formed to establish the etiology of an effusion, although only the mainstay of medical management for cardiac tamponade.
after thorough noninvasive workup is completed before con- These measures are largely ineffective and should be used only
sideration of an invasive procedure [1]. While the etiology of as a bridge to pericardial drainage [9,10]. The exact method
effusions varies widely in the literature depending upon patient and timing of pericardiocentesis is ultimately dictated by the
population, a diagnosis based on initial examination alone was patients overall degree of instability. While echocardiographic
highly predictive of effusion etiology in one study [2]. In an- and fluoroscopic guidance is preferred, unguided (or blind)
other large series of patients, between 50% and 60% of mod- pericardiocentesis may be required in patients with severe hy-
erate to large effusions were due to a previously established potension not responsive to temporizing measures. In this set-
medical condition [3]. In addition, the clinical context in which ting, there are no absolute contraindications to the proce-
diagnostic pericardiocentesis is performed affects its predictive dure, and it should be performed without delay at the patients
value, with greater diagnostic yield for large effusions than bedside.
for acute pericarditis [46]. Primarily due to the routine use Urgent pericardiocentesis is indicated for patients with an
of echocardiographic guidance, the major (1.2%) and minor established effusion who are initially hypotensive but respond
(3.5%) complications of pericardiocentesis have significantly quickly to hemodynamic support. Unlike acute tamponade,
decreased over the past several decades, with successful single subacute tamponade is more likely to present with protean
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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78 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

symptoms such as dyspnea and fatigue. Patients with preex- of 2,000 mL or greater may accumulate without significant
isting hypertension may not demonstrate severe hypotension hemodynamic compromise. As a result, chronic effusions may
due to a persistent sympathetic response. Echocardiographic present with symptoms such as cough, dyspnea, dysphagia, or
assessment of effusion size, hemodynamic impact, and optimal early satiety owing to compression of adjacent thoracic struc-
percutaneous approach are of paramount importance [11]. tures. Conversely, intravascular hypovolemia, impaired ven-
The procedure should be performed within several hours of tricular systolic function, and ventricular hypertrophy with
presentation while careful monitoring and support continue. decreased elasticity of the myocardium (diastolic dysfunction)
As in elective circumstances, pericardiocentesis in these pa- may exacerbate hemodynamic compromise without significant
tients should be undertaken with appropriate visual guidance, effusions present.
the method of which depends on the physicians expertise and
resources.
Three additional points must be stressed regarding pa- PROCEDURE
tients undergoing expedited pericardiocentesis. First, coagu-
lation parametersprothrombin time, partial thromboplastin Since the first blind (or closed) pericardiocentesis performed
time, and platelet count (>50,000 per L)should be checked in 1840 [16], numerous approaches to the pericardial space
and, when possible, quickly normalized prior to the procedure. have been described. Marfan [17] performed the subcostal ap-
If clinically feasible, the procedure should be postponed until proach in 1911, which then became the standard approach for
the international normalized ratio is less than 1.4. An anti- unguided pericardiocentesis as it is extrapleural and avoids the
Xa level is recommended for patients receiving low-molecular- coronary and internal mammary arteries.
weight heparin. For emergent pericardiocentesis performed on The advent of clinically applicable ultrasonography has
anticoagulant therapy, prolonged and continuous drainage is opened a new chapter in diagnostic and therapeutic approaches
recommended. Second, many critical care specialists and car- to pericardial disease, allowing clinicians to quantitate and lo-
diologists advocate performance of all pericardiocentesis pro- calize pericardial effusions quickly and noninvasively [18,19].
cedures in the catheterization laboratory with concomitant Callahan et al. [20,21] at the Mayo Clinic established the effi-
right heart pressure monitoring to document efficacy of the cacy and safety of two-dimensional echocardiography to guide
procedure and to exclude a constrictive element of pericar- pericardiocentesis. While direct quantification of total fluid ac-
dial disease, although excessive delays must be avoided (see cumulation with echo is not yet possible, circumferential ef-
Chapter 34). Finally, efforts to ensure a cooperative and sta- fusions of more than 10 mm are considered large (500 mL),
tionary patient during the procedure greatly facilitate the per- and the ESC recommends pericardiocentesis of effusions of
formance, safety, and success of pericardiocentesis. more than 20 mm, regardless of the presence of hemody-
The clinical presentation of hemodynamically significant namic compromise (class IIa indication) [8]. Typically, at least
pericardial effusions varies widely among patients. A compre- 250 mL of fluid is required for safe pericardiocentesis. The rou-
hensive understanding requires knowledge of normal pericar- tine use of echocardiography has resulted in two major trends
dial anatomy and physiology. in clinical practice: First, two-dimensional echocardiography is
commonly used to guide pericardiocentesis, with success rates
comparable to those of traditionally fluoroscopic-guided pro-
ANATOMY cedures [2224]. Second, approaches other than the traditional
subxiphoid method have been investigated owing to the abil-
The pericardium is a membranous structure with two layers: ity to clearly define the anatomy (location and volume) of each
the visceral and parietal pericardium. The visceral pericardium patients effusion [20,21]. In one series of postsurgical patients,
is a monolayer of mesothelial cells adherent to the epicardial the subxiphoid approach was the most direct route in only 12%
surface by a loose collection of small blood vessels, lymphatics, of effusions [25]. With the use of echo guidance, apical pericar-
and connective tissue. The parietal pericardium is a relatively diocentesis and parasternal pericardiocentesis are increasingly
inelastic 2 mm dense outer network of collagen and elastin performed with success rates comparable to those of the subx-
with an inner surface of mesothelial cells. It is invested around iphoid approach. In the apical approach, the needle is directed
the great vessels and defines the shape of the pericardium, with parallel to the long axis of the heart toward the aortic valve.
attachments to the sternum, diaphragm, and anterior medi- Parasternal pericardiocentesis is performed with needle inser-
astinum while anchoring the heart in the thorax [12]. Pos- tion 1 cm lateral to the sternal edge to avoid internal mam-
teriorly, the visceral epicardium is absent, with the parietal mary laceration. All approaches employ a Seldinger technique
epicardium attached directly to the heart at the level of the of over-the-wire catheter insertion. As the subxiphoid approach
vena cavae [13]. The potential space between the visceral and remains the standard of practice and is the preferred approach
parietal mesothelial cell layers normally contains 15 to 50 mL for unguided emergent pericardiocentesis, it will be described
of serous fluid, which is chemically similar to plasma ultrafil- later.
trate, in the atrioventricular (AV) and interventricular grooves Regardless of the approach used, confirmation of appropri-
[14]. The pericardium is relatively avascular, but is well inner- ate positioning is mandatory and preferably performed before a
vated and may produce significant pain with vagal responses dilation catheter is advanced over the wire. Direct visualization
during procedural manipulation or inflammation [15]. of the needle with either echocardiography or fluoroscopy and
Because of the inelastic physical properties of the peri- injection of agitated saline (echo guided) or a small amount of
cardium, the major determinant of when and how pericar- contrast (fluoroscopy guided) should be performed to confirm
dial effusions come to clinical attention is directly related to the correct position. Contrast layering inferiorly and not enter-
the speed of accumulation. Effusions that collect rapidly (over ing circulation or causing a myocardial stain confirms correct
minutes to hours) may cause hemodynamic compromise with positioning.
volumes of 250 mL or less. These effusions are usually located In addition to two large-bore peripheral intravenous lines
posteriorly and are often difficult to detect without echocar- for aggressive resuscitative efforts, standard electrocardio-
diography or other imaging modalities such as multislice com- graphic monitoring is mandatory. Historically, an electro-
puted tomography or cardiac magnetic resonance imaging . cardiographic (ECG) lead directly attached to the puncture
In contrast, effusions developing slowly (over days to weeks) needle has been used to detect contact with the myocardium
allow for dilation of the fibrous parietal membrane. Volumes via the appearance of a large injury current (ST elevation).
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 7: Pericardiocentesis 79

TA B L E 7 . 1
MATERIALS FOR PERCUTANEOUS
PERICARDIOCENTESIS

Site preparation
Antiseptic
Gauze
Sterile drapes and towels
Sterile gloves, masks, gowns, caps
5-mL or 10-mL syringe with 25-gauge needle
1% lidocaine (without epinephrine)
Code cart
Atropine (1-mg dose vial)
Procedure
No. 11 blade
20-mL syringe with 10 mL of 1% lidocaine (without
epinephrine)
18-gauge, 8-cm, thin-walled needle with blunt tip
Multiple 20- and 40-mL syringes
Hemostat
Electrocardiogram machine
Three red-top tubes
Two purple-top (heparinized) tubes
Culture bottles
Postprocedure
Suture material
Scissors
Sterile gauze and bandage
FIGURE 7.1. Materials required for pericardiocentesis (clockwise
from upper left): 1% lidocaine solution, suture material, 10-mL sy-
ringe with 25-gauge needle, 10-mL syringe with 22-gauge needle, no.
Because a suboptimally grounded needle could fibrillate the 11 blade, 18-gauge 8-cm thin-walled needle, 20-mL syringe, 30-mL
heart (and the widespread availability of echocardiography), syringe, alligator clip, hemostat, three red-top tubes, two purple-top
many cardiologists have abandoned this practice and the 2004 tubes, culture bottles, scissors.
ESC guidelines consider it an inadequate safeguard [8,26].
The materials required for bedside pericardiocentesis are
listed in Table 7.1 (Fig. 7.1). Table 7.2 (Fig. 7.2) lists the mate- cutaneous wheal by infiltrating the needle entry site with 1%
rials required for simultaneous placement of an intrapericardial lidocaine solution (without epinephrine). To facilitate nee-
drainage catheter. The materials are available in prepackaged dle entry, incise the skin with a no. 11 blade at the selected
kits or individually. site after achieving adequate local anesthesia.
The subxiphoid approach for pericardiocentesis is as 4. Insertion of the needle apparatus. The angle of entry with
follows: respect to the skin should be approximately 45 degree in
1. Patient preparation. Assist the patient in assuming a com- the subxiphoid area. Direct the needle tip superiorly, aim-
fortable supine position with the head of the bed elevated ing for the patients left shoulder. Continue to advance the
to approximately 45 degree from the horizontal plane. Ex- needle posteriorly while alternating between aspiration and
tremely dyspneic patients may need to be positioned fully
upright, with a wedge if necessary. Elevation of the thorax
allows free-flowing effusions to collect inferiorly and ante- TA B L E 7 . 2
riorly, sites that are safest and easiest to access using the
subxiphoid approach. MATERIALS FOR INTRAPERICARDIAL CATHETER
2. Needle entry site selection. Locate the patients xiphoid pro-
cess and the border of the left costal margin using inspection Catheter placement
and careful palpation. The needle entry site should be 0.5 Teflon-coated flexible J-curved guidewire
cm to the (patients) left of the xiphoid process and 0.5 to 6 Fr dilator
1.0 cm inferior to the costal margin (Fig. 7.3). It is help- 8 Fr dilator
ful to estimate (by palpation) the distance between the skin 8 Fr, 35-cm flexible pigtail catheter with multiple
surface and the posterior margin of the bony thorax: This fenestrations (end and side holes)
helps guide subsequent needle insertion. The usual distance Drainage systema
is 1.0 to 2.5 cm, increasing with obesity or protuberance of Three-way stopcock
the abdomen. Sterile intravenous tubing
3. Site preparation. Strict sterile techniques must be main- 500-mL sterile collecting bag (or bottle)
tained at all times in preparation of the needle entry site. Sterile gauze and adhesive bag (or bottle)
Prepare a wide area in the subxiphoid region and lower Suture material
thorax with a chlorhexidine solution. Use maximum bar-
rier precautions and use a large fenestrated drape to cover a
System described allows continuous drainage.
the field. After performing a time out, raise a 1- to 2-cm sub-
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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80 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

FIGURE 7.4. Needle direction. The needle tip should be reduced to


15 degree once the posterior margin of the bony thorax has been
passed. Needle advancement: The needle is advanced toward the left
shoulder slowly while alternating between aspiration and injection.
A give is felt, and fluid is aspirated when the pericardial space is
entered.

5. Needle direction. Once under the costal margin, reduce the


angle of contact between the needle and skin to 15 degree:
This will be the angle of approach to the pericardium; the
needle tip, however, should still be directed toward the pa-
tients left shoulder. A 15-degree angle is used regardless of
FIGURE 7.2. Materials required for intrapericardial catheter place- the height of the patients thorax (whether at 45 degree or
ment and drainage (clockwise from lower left): Teflon-coated flexible sitting upright) (Fig. 7.4).
0.035-in J-curved guidewire, 8 Fr dilator, 6.3 Fr dilator, 8 Fr catheter
with end and side holes (35-cm flexible pigtail catheter not shown),
6. Needle advancement. Advance the needle slowly while al-
three-way stopcock, 500-mL sterile collecting bag and tubing, suture ternating between aspiration of the syringe and injection
material. of 1% lidocaine solution. Obtain a baseline lead V trac-
ing and monitor a continuous ECG tracing for the presence
of ST-segment elevation or premature ventricular contrac-
tions (evidence of epicardial contact) as the needle is ad-
injection of lidocaine (with a half-filled 20-mL syringe of vanced. Advance the needle along this extrapleural path
1% lidocaine), until the tip has passed just beyond the pos- until either
terior border of the bony thorax (Fig. 7.3). The posterior a. a give is felt, and fluid is aspirated from the pericardial
border usually lies within 2.5 cm of the skin surface. If the space (usually 6.0 to 7.5 cm from the skin) (Fig. 7.4).
needle tip contacts the bony thorax, inject lidocaine after Some patients may experience a vasovagal response at
aspirating to clear the needle tip and anesthetize the perios- this point and require atropine intravenously to increase
teum. Then, walk the needle behind the posterior (costal) their blood pressure and heart rate or
margin. b. ST-segment elevation or premature ventricular contrac-
tions are observed on the electrocardiographic lead V
tracing when the needle tip contacts the epicardium.
If ST-segment elevation or premature ventricular com-
plexes occur, immediately (and carefully) withdraw the
needle toward the skin surface while aspirating. Avoid
any lateral motion, which could damage the epicardial
vessels. Completely withdraw the needle if no fluid is ob-
tained during the initial repositioning.
If sanguineous fluid is aspirated, the differentiation be-
tween blood and effusion must be made immediately.
In addition to confirming catheter position by saline or
contrast as described above (or pressure transduction), sev-
eral milliliters of fluid can be placed on a gauze and ob-
served for clotting. Intrinsic fibrinolytic activity in the peri-
cardium prevents subacute/chronic effusions from clotting,
where frank hemorrhage or intraventricular blood will over-
whelm fibrinolysis.
The patients hemodynamic status should improve
FIGURE 7.3. Insertion of the needle apparatus. After the subxiphoid
promptly with removal of sufficient fluid. Successful relief of
region and lower thorax are prepared and adequate local anesthesia tamponade is supported by (a) a fall in intrapericardial pres-
is given, the pericardiocentesis needle is inserted in the subxiphoid sure to levels between 3 and +3 mm Hg, (b) a fall in right
incision. The angle of entry (with the skin) should be approximately atrial pressure and a separation between right and left ven-
45 degree. The needle tip should be directed superiorly, toward the tricular diastolic pressures, (c) augmentation of cardiac out-
patients left shoulder. put, (d) increased systemic blood pressure, and (e) reduced
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 7: Pericardiocentesis 81

TA B L E 7 . 3
DIAGNOSTIC STUDIES PERFORMED ON
PERICARDIAL FLUID

Hematocrit
White blood cell count with differential
Glucose
Protein
Grams stain
Routine aerobic and anaerobic cultures
Smear and culture for acid-fast bacilli
Cytology
Cholesterol, triglyceride
Amylase
Lactate dehydrogenase
Special cultures (viral, parasite, fungal)
Antinuclear antibody
Rheumatoid factor
Total complement, C3

pulsus paradoxus to physiologic levels (10 mm Hg or less).


An improvement may be observed after removal of the first FIGURE 7.5. Placement technique. Holding the needle in place, a
Teflon-coated, 0.035-in guidewire is advanced into the pericardial
50 to 100 mL of fluid. If the right atrial pressure remains
space. The needle is then removed. After a series of skin dilations,
elevated after fluid removal, an effusive-constrictive process an 8Fr, 35-cm flexible pigtail catheter is placed over the guidewire into
should be considered. The diagnostic studies performed on the pericardial space. Passage of dilators and the pigtail catheter is
pericardial fluid are outlined in Table 7.3. Several options facilitated by a gentle clockwise/counterclockwise motion.
exist for continued drainage of the pericardial space. The
simplest approach is to use large-volume syringes and aspi-
rate the fluid by hand. This approach is not always practi-
cal (i.e., in large-volume effusions), however, and manipula- catheter should be flushed manually every 4 to 6 hours using
tion of the needle apparatus may cause myocardial trauma. 10 to 15 cc of normal saline solution until volume of aspiration
Alternatively, most pericardiocentesis kits include materi- falls to less than 25 mL per day [30].
als and instructions for a catheter-over-needle technique for
inserting an indwelling pericardial drain via the Seldinger
technique.
7. Pericardial drain Placement (Fig. 7.5). Create a track for
the catheter by passing a 6 French (Fr) dilator over a firmly SHORT-TERM AND LONG-TERM
held guidewire. After removing the dilator, use the same MANAGEMENT
technique to pass an 8 Fr dilator. Then advance an 8 Fr
flexible pigtail (or side hole) catheter over the guidewire After pericardiocentesis, close monitoring is required to de-
into the pericardial space. Remove the guidewire. Passage tect evidence of recurrent tamponade and procedure-related
of the dilators is facilitated by use of a torquing (clock- complications. Table 7.4 lists the most common serious com-
wise/counterclockwise) motion. Proper positioning of the plications associated with pericardiocentesis [1,8,31,32]. Fac-
catheter using radiography, fluoroscopy, or bedside echocar- tors associated with an increased risk of complications include
diography can be used to facilitate fluid drainage. (a) small effusion (less than 250 mL), (b) posterior effusion,
8. Drainage system [27,28]. Attach a three-way stopcock to (c) loculated effusion, (d) maximum anterior clear space (by
the intrapericardial catheter and close the system by attach- echocardiography) less than 10 mm, and (e) unguided percu-
ing the stopcock to the sterile collecting bag with the con- taneous approach. All patients undergoing pericardiocentesis
necting tubing. The catheter may also be connected to a should have a portable chest radiograph performed immedi-
transducer, allowing intrapericardial pressure monitoring. ately after the procedure to exclude the presence of pneu-
The system may be secured as follows: mothorax. A transthoracic two-dimensional echocardiogram
a. Suture the pigtail catheter to the skin, making sure the should be obtained within several hours to evaluate the ade-
lumen is not compressed. Cover the entry site with a quacy of pericardial drainage and confirm catheter placement.
sterile gauze and dressing. As pericardiocentesis typically does not remove all of the ef-
b. Secure the drainage bag (or bottle) using tape at a level fusion (and active bleeding or secretion may occur), the peri-
approximately 35 to 50 cm below the level of the heart. cardial catheter is typically left in for 24 to 72 hours or until
Echocardiography or fluoroscopic guidance may be used drainage subsides. Extended catheter drainage is safe and is
to reposition the pigtail catheter, facilitating complete associated with a trend toward lower recurrence rates over a
drainage of existing pericardial fluid. 4-year follow-up [30]. Catheter drainage of more than 100 mL
per day after 3 days may need to be considered for surgical
It is recommended to drain fluid in sequential steps of less intervention, sclerosing agents, or percutaneous balloon peri-
than 1,000 mL to avoid acute right-ventricular dilationa rare cardotomy.
but serious complication [8,29]. Drainage is recommended un- The long-term management of patients with significant peri-
til pericardial pressure is subatmospheric with inspiration. The cardial fluid collections is beyond the scope of this chapter
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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82 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 7 . 4 TA B L E 7 . 5
COMPLICATIONS OF PERICARDIOCENTESIS COMMON CAUSES OF PERICARDIAL EFFUSION

Cardiac puncture with hemopericardium Idiopathic


Coronary artery laceration (hemopericardium or myocardial Malignancy (primary, metastatic; solid tumors, hematologic)
infarction) Uremia
Pneumothorax Graft versus host disease
Hemothorax Extramedullary hematopoiesis
Arrhythmias Postpericardiotomy syndrome
Bradycardia Connective tissue disease
Ventricular tachycardia/ventricular fibrillation Trauma
Trauma to abdominal organs (liver, gastrointestinal tract) Blunt
Hemorrhagic peritonitis Penetrating
Cardiac arrest (predominantly pulseless electrical activity from Infection
myocardial perforation, but occasionally tachyarrhythmia or Viral (including HIV)
bradyarrhythmia)a Bacterial
Transient biventricular dysfunction Fungal
Infection Tuberculosis
Fistula formation Aortic dissection
Pulmonary edema Complication of cardiac catheterization, percutaneous
coronary intervention, or pacemaker insertion
a
Incidence has varied from 0% to 5% in studies and was less common Myxedema
in guided procedures, more common in blind procedures. Postirradiation
Permayer-Miulda G, Sagrista- Savleda J, Soler-Soler J: Primary acute
pericardial disease: a prospective study of 231 consecutive patients.
Am J Cardiol 56:623, 1985.
Wong B, Murphy J, Chang CJ, et al: The risk of pericardiocentesis.
Am J Cardiol 44:1110, 1979.
Krikorian JG, Hancock EW: Pericardiocentesis. Am J Med 65:808, ing the preferred treatment. Aggressive attempts at nonsurgical
1978. management of chronically debilitated patients or those with
metastatic disease involving the pericardium may be appropri-
ate [33,34]. Percutaneous balloon pericardotomy or pericar-
dial sclerosis with tetracycline, cisplatin, and other agents has
(see Chapter 34); however, the indications for surgical benefited carefully selected patients with malignant pericardial
intervention have been reviewed briefly earlier in the chapter. disease [3537]. Patients with a guarded prognosis who fail
The etiology of the pericardial effusion (Table 7.5) and the pa- aggressive medical therapy should be offered the least invasive
tients functional status are of central importance for determin- procedure.

References
1. Permayer-Miulda G, Sagrista-Sauleda J, Soler-Soler J: Primary acute pericar- 13. Roberts WC, Spray TL: Pericardial heart disease: a study of its causes, conse-
dial disease: a prospective study of 231 consecutive patients. Am J Cardiol quences, and morphologic features, in Spodick D (ed): Pericardial Diseases.
56:623, 1985. Philadelphia, FA Davis, 1976, p 17.
2. Levy PY, Corey R, Berger P, et al: Etiologic diagnosis of 204 pericardial 14. Shabatai R: Function of the pericardium, in Fowler NO (ed): The Peri-
effusions. Medicine (Baltimore) 82:385, 2003. cardium in Health and Disease. Mount Kisco, NY, Futura, 1985, p 19.
3. Sagrista-Sauleda J, Merce J, Permanyer-Miralda G, et al: Clinical clues to the 15. Little W, Freeman G: Pericardial disease. Circulation 113:16221632,
causes of large pericardial effusions. Am J Med 109:95, 2000. 2006.
4. Corey GR, Campbell PT, van Trigt P, et al: Etiology of large pericardial 16. Schuh R: Erfahrungen uber de Paracentese der Brust und des Herz Beutels.
effusions. Am J Med 95:209, 1993. Med Jahrb Osterr Staates Wien 33:388, 1841.
5. Permanyer-Miralda G, Sagrista-Sauleda J, Soler-Soler J. Primary acute peri- 17. Marfan AB: Poncitian du pericarde par l espigahe. Ann Med Chir Infarct
cardial disease: a prospective series of 231 consecutive patients. Am J Cardiol 15:529, 1911.
56:623, 1985. 18. Tibbles CD, Porcaro W: Procedural applications of ultrasound. Emerg Med
6. Zayas R, Anguita M, Torres F, et al: Incidence of specific etiology and role Clin North Am 22:797, 2004.
of methods for specific etiologic diagnosis of primary acute pericarditis. Am 19. Rifkin RD, Mernoff DB: Noninvasive evaluation of pericardial effusion com-
J Cardiol 75:378, 1995. position by computed tomography. Am Heart J 149:1120, 2005.
7. Quinones M, Douglas P, Foster E, et al: ACC/AHA clinical competence state- 20. Callahan JA, Seward JB, Nishimura RA: 2-dimensional echocardiography-
ment on echocardiography: a report of the American College of Cardiol- guided pericardiocentesis: experience in 117 consecutive patients. Am J Car-
ogy/American Heart Association/American College of Physicians-American diol 55:476, 1985.
Society of Internal Medicine Task Force on Clinical Competence. J Am Coll 21. Callahan JA, Seward JB, Tajik AJ: Pericardiocentesis assisted by
Cardiol 41(4):687708, 2003. 2-dimensional echocardiography. J Thorac Cardiovasc Surg 85:877,
8. Maisch B, Seferovic PM, Ristic AD, et al: Guidelines on the diagnosis and 1983.
management of pericardial diseases. The task force on the diagnosis and 22. Tsang TSM, Freeman WK, Sinak LJ, et al: Echocardiographically guided
management of pericardial diseases of the European Society of Cardiology. pericardiocentesis: evolution and state-of-the-art technique. Mayo Clin Proc
Eur Heart J 25(7):587610, 2004. 73:647, 1998.
9. Callahan M: Pericardiocentesis in traumatic and non-traumatic cardiac tam- 23. Callahan JA, Seward JB, Tajik AJ: Cardiac tamponade: pericardiocentesis
ponade. Ann Emerg Med 13:924, 1984. directed by two-dimensional echocardiography. Mayo Clin Proc 60:344,
10. Spodick DH: Medical treatment of cardiac tamponade, in Caturelli G (ed): 1985.
Cura Intensive Cardiologica. Rome, TIPAR Poligrafica, 1991, pp 265 24. Tsang TS, Enriquez-Sarano M, Freeman WK, et al: Consecutive 1127 thera-
268. peutic echocardiographically guided pericardiocentesis: clinical profile, prac-
11. Cheitlin MD, Armstrong WF, Aurigemma GP, et al: ACC/AHA/ASE 2003 tice patterns, and outcomes spanning 21 years. Mayo Clin Proc 77:429,
guideline for the clinical application of echocardiography. J Am Coll Cardiol 2002.
42(5):954970, 2003. 25. Fagan S, Chan KL: Pericardiocentesis. Chest 116:275276, 1999.
12. Spodick DH: Macrophysiology, microphysiology, and anatomy of the peri- 26. Tweddell JS, Zimmerman AN, Stone CM, et al: Pericardiocentesis guided by
cardium: a synopsis. Am Heart J 124:10461051, 1992. a pulse generator. J Am Coll Cardiol 14(4):10741083, 1989.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 8: Chest Tube Insertion and Care 83

27. Kapoor AS: Technique of pericardiocentesis and intrapericardial drainage, 33. Shepherd FA, Morgan C, Evans WK, et al: Medical management of malig-
in Kapoor AS (ed): International Cardiology. New York, Springer-Verlag, nant pericardial effusion by tetracycline sclerosis. Am J Cardiol 60:1161,
1989, p 146. 1987.
28. Patel AK, Kogolcharoen PK, Nallasivan M, et al: Catheter drainage of 34. Morm JE, Hallonby D, Gonda A, et al: Management of uremia pericarditis:
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92:1018, 1987. Ann Thorac Surg 22:588, 1976.
29. Armstrong WF, Feigenbaum H, Dillon JC: Acute right ventricular dilation 35. Reitknecht F, Regal AM, Antkowiak JG, et al: Management of cardiac tam-
and echocardiographic volume overload following pericardiocentesis for re- ponade in patients with malignancy. J Surg Oncol 30:19, 1985.
lief of cardiac tamponade. Am Heart J 107:12661270, 1984. 36. Maisch B, Ristic AD, Pankuweit S, et al: Neoplastic pericardial effusion.
30. Tsang TS, Barnes ME, Gersh BJ, et al: Outcomes of clinically significant idio- Efficacy and safety of intrapericardial treatment with cisplatin. Eur Heart J
pathic pericardial effusion requiring intervention. Am J Cardiol 91(6):704 23:1625, 2002.
707, 2002. 37. Ziskind AA, Pearce AC, Lemon CC, et al: Percutaneous balloon pericar-
31. Wong B, Murphy J, Chang CJ, et al: The risk of pericardiocentesis. Am J diotomy for the treatment of cardiac tamponade and large pericardial effu-
Cardiol 44:1110, 1979. sions: description of technique and report of the first 50 cases. J Am Coll
32. Krikorian JG, Hancock EW: Pericardiocentesis. Am J Med 65: 808, 1978. Cardiol 21:15, 1993.

CHAPTER 8 CHEST TUBE INSERTION


AND CARE
ULISES TORRES AND ROBERT A. LANCY

Chest tube insertion involves placement of a sterile tube into


the pleural space to evacuate air or fluid into a closed collec- CHEST TUBE PLACEMENT
tion system to restore negative intrathoracic pressure, promote
lung expansion, and prevent potentially lethal levels of pres- Indications
sure from developing in the thorax. In order to avoid all the
potential life-threatening complications that can result from The indications for closed intercostal drainage include a va-
the insertion of a chest tube, a clear concept of physiopathol- riety of disease processes in the hospital setting (Table 8.1).
ogy and anatomy has to be established, followed by a visual- The procedure may be performed to palliate a chronic disease
ization of the different steps in order to proceed with a safe process or to relieve an acute, life-threatening process. Chest
practice [1]. tubes also may provide a vehicle for pharmacologic interven-
tions, as when used with antibiotic therapy for treatment of an
empyema or instillation of sclerosing agents to prevent recur-
rence of malignant effusions.
PLEURAL ANATOMY AND
Pneumothorax
PHYSIOLOGY
Accumulation of air in the pleural space is the most common
The pleural space is a potential space that separates the vis- indication for chest tube placement. Symptoms include tachyp-
ceral and parietal pleura with a thin layer of lubricating fluid. nea, dyspnea, and pleuritic pain, although some patients (in
Although up to 500 mL per day may enter the pleural space, particular, those with a small spontaneous pneumothorax) may
0.1 to 0.2 mL per kg surrounds each lung in the pleural space at be asymptomatic. Physical findings include diminished breath
any given time. These two layers are lined by an extensive lym- sounds and hyperresonance to percussion on the affected
phatic network that ultimately drains into the thoracic duct via side.
the mediastinal and intercostal lymph nodes. These lymphatics Diagnosis is often confirmed by chest radiography. The size
prevent the accumulation of this pleural fluid. It is estimated of a pneumothorax may be estimated, but this is at best a
that this mechanism allows clearance of up to 20 mL per hour rough approximation of a three-dimensional space using a two-
per hemithorax of pleural fluid in a 70-kg human. The elastic dimensional view. Although the gold standard for the identifi-
recoil of the chest wall and lung creates a subatmospheric pres- cation of a pneumothorax (independent of location within the
sure in the space, between 5 and 10 cm H2 O, which binds thorax) is a computed tomography (CT) scan of the chest, ul-
the lung to the chest wall [2,3]. trasound (US) identification has been shown to have the same
Drainage of the pleural space is necessary when the normal sensitivity as that of a CT scan. Furthermore, US estimates of
physiologic processes are disrupted by increased fluid entry into the extension of the pneumothorax correlate well with CT scan
the space due to alterations in hydrostatic pressures (e.g., con- [4]. The sensitivity of detecting a pneumothorax with US ranges
gestive heart failure) or oncotic pressures or by changes in the from 86% to 89%, compared to a range of 28% to 75% with
parietal pleura itself (e.g., inflammatory diseases). A derange- a supine chest X-ray [46].
ment in lymphatic drainage, as with lymphatic obstruction by The decision to insert a chest tube for a pneumothorax is
malignancy, may also result in excess fluid accumulation and based on the patients overall clinical status and may be aided
disruption of the pleural and lung parenchymal anatomy, cre- by serial chest radiographs. Tube decompression is indicated
ating accumulation of air and/or blood. in those who are symptomatic, who have a large or expanding
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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84 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 8 . 1 ternal mammary arteries or to the pulmonary parenchyma. Up


to a third of patients with traumatic rib fractures may have an
INDICATIONS FOR CHEST TUBE INSERTION accompanying pneumothorax or hemothorax [8]. Pulmonary
parenchymal bleeding from chest trauma is often self-limited
Pneumothorax due to the low pressure of the pulmonary vascular system.
Primary or spontaneous However, systemic sources (intercostal, internal mammary or
Secondary subclavian arteries, aorta, or heart) may persist and become
Chronic obstructive pulmonary disease life threatening.
Pneumonia Indications for open thoracotomy in the setting of traumatic
Abscess/empyema hemothorax include initial blood loss greater than 1,500 mL
Malignancy or continued blood loss exceeding 500 mL over the first hour,
Traumatic 200 mL per hour after 2 to 4 hours, or 100 mL per hour after
Iatrogenic 6 to 8 hours, or in an unstable patient who does not respond
Central line placement to volume resuscitation [911]. Placement of large-bore [36 to
Positive-pressure ventilation 40 French (Fr)] drainage tubes encourages evacuation of blood
Thoracentesis and helps determine the need for immediate thoracotomy.
Lung biopsy Spontaneous pneumothoraces may result from necrotiz-
Hemothorax ing pulmonary infections, pulmonary arteriovenous malfor-
Traumatic mations, pulmonary infarctions, primary and metastatic ma-
Blunt lignancies of the lung and pleura, and tearing of adhesions
Penetrating (trauma or biopsy) between the visceral and parietal pleurae.
Iatrogenic
Malignancy
Empyema
Pulmonary arteriovenous malformation Empyemas are pyogenic infections of the pleural space that
Blood dyscrasias may result from numerous clinical conditions, including necro-
Ruptured thoracic aortic aneurysm tizing pneumonia, septic pulmonary emboli, spread of intra-
Empyema abdominal infections, or inadequate drainage of a traumatic
Parapneumonic hemothorax. Pyothorax as a complication of pneumonia is
Posttraumatic less common now than in the preantibiotic era, with the com-
Postoperative mon organisms now being Staphylococcus aureus and anaero-
Septic emboli bic and gram-negative microbes.
Intra-abdominal infection Definitive management includes evacuation of the collec-
tion and antibiotic therapy. Large-bore drainage tubes (36 to
Chylothorax 40 Fr) are used, and success is evidenced by resolving fever
Traumatic and leukocytosis, improving clinical status, and eventual re-
Surgical solving drainage. The tube can then be removed slowly over
Congenital several days, allowing a fibrous tract to form. If no improve-
Malignancy ment is seen, rib resection and open drainage may be indi-
Pleural effusion cated. Chronic empyema may require decortication or, in more
Transudate debilitated patients, open-flap drainage (Eloesser procedure).
Exudate (malignancy, inflammatory) Fibrinolytic enzymes (urokinase or streptokinase) can also be
instilled through the tube to facilitate drainage of persistent
purulent collections or for hemothorax or malignant effusions
[1214].
pneumothorax, who are being mechanically ventilated (the lat-
ter of whom may present acutely with deteriorating oxygena-
Chylothorax
tion and an increase in airway pressures, necessitating immedi- A collection of lymphatic fluid in the pleural space is termed
ate decompression), or in patients where there is no capability chylothorax. Because of the immunologic properties of lymph,
for serial chest radiographs or the absence of trained person- the collection is almost always sterile. As much as 1,500 mL
nel (off-hour shifts and geographic location) for the emergency per day may accumulate and may result in hemodynamic com-
placement of a chest tube [3]. promise or adverse metabolic sequelae as a result of loss of
A small, stable, asymptomatic pneumothorax can be fol- protein, fat, and fat-soluble vitamins. The diagnosis is con-
lowed with serial chest radiographs. Reexpansion occurs at firmed by a fluid triglyceride level greater than 110 mg per
the rate of approximately 1.25% of lung volume per day [7]. dL or a cholesteroltriglyceride ratio of less than 1 [15,16].
Persistent leaking of air into the pleural space with no route Primary causes of chylothorax include trauma, surgery, malig-
of escape will ultimately collapse the affected lung, flatten the nancy, and congenital abnormalities [17].
diaphragm, and eventually produce contralateral shift of the Treatment involves tube drainage along with aggressive
mediastinum. Compression of the contralateral lung and com- maintenance of volume and nutrition. With central parenteral
promise of venous return result in progressive hypoxemia and nutrition and intestinal rest (to limit flow through the thoracic
hypotension. Emergency decompression with a 14- or 16-gauge duct), approximately 50% will resolve without surgery [18].
catheter in the midclavicular line of the second intercostal space Open thoracotomy may be necessary to ligate the duct and
may be lifesaving while preparations for chest tube insertion close the fistula; in the cases when the abdominal lymphatics
are being made. are patent, percutaneous catheterization and embolization of
the thoracic duct can be perform with good results [19].
Hemothorax
Accumulation of blood in the pleural space can be classified as
Pleural Effusion
spontaneous, iatrogenic, or traumatic. Attempted thoracentesis Management of a pleural effusion often begins with thora-
or tube placement may result in injury to the intercostal or in- centesis to identify the collection as either a transudative or
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Chapter 8: Chest Tube Insertion and Care 85

exudative process. Treatment of transudative pleural effusions TA B L E 8 . 2


is aimed at controlling the underlying cause (e.g., congestive
heart failure, nephrotic syndrome, and cirrhosis). Tube thora- CHEST TUBE INSERTION EQUIPMENT
costomy may be helpful in controlling a temporary ventilatory
or compliance-related issue, but it is not usually the solution. Chlorhexidine or povidoneiodine solution
Exudative pleural effusions, however, often require tube Sterile towels and drapes with full body cover
drainage. Sterile sponges
Sometimes it is necessary to perform chemical pleurodesis 1% lidocaine without epinephrine (40 mL)
in order to develop apposition of pleural surfaces. Agents that 10-mL syringe
can be used include bleomycin, doxycycline, and talc [2022]. 18-, 21-, and 25-gauge needles
2 Kelly clamps, one large and one medium
Mayo scissors
Standard tissue forceps
CONTRAINDICATIONS Towel forceps
Needle holder
Large bullous disease of the lung may be mistaken for a pneu- 0-Silk suture with cutting needle
mothorax, a circumstance in which attempted pleural tube Scalpel handle and no. 10 blade
placement may result in significant morbidity. CT scanning Chest tubes (24, 28, 32, and 36 Fr)
is indicated in these instances to clearly analyze the anatomy. Chest tube drainage system (filled appropriately)
Likewise, an apparent pleural effusion may be a lung abscess Petrolatum gauze
or consolidated pulmonary parenchyma (e.g., pneumonia 2-in. nonelastic adhesive tape
and atelectasis). Again, CT scanning or ultrasonography may Sterile gowns and gloves, masks, caps
prove to be helpful in delineating the pathology before tube
placement.
History of a process that will promote pleural symphysis
(such as a sclerosing procedure, pleurodesis, pleurectomy, or
Careful titration of parenteral narcotics or benzodiazepines
previous thoracotomy on the affected side) should raise caution
and careful, generous administration of local anesthetic agents
and prompt evaluation with CT scanning to help identify the
provide for a relatively painless procedure. Standard, large-
exact area of pathology and to direct tube placement away
bore drainage tubes are made from either Silastic or rubber.
from areas where the lung is adherent to the chest wall. In a
Silastic tubes are either right angled or straight, have multiple
postpneumonectomy patient, the pleural tube should be placed
drainage holes, and contain a radiopaque stripe with a gap to
above the original incision, as the diaphragm frequently rises
mark the most proximal drainage hole. They are available in
to this height.
sizes ranging from 6 to 40 Fr, with size selection dependent on
The possibility of herniation of abdominal contents through
the patient population (6 to 24 Fr for infants and children) and
the diaphragm in patients with severe blunt abdominal trauma
the collection being drained (24 to 28 Fr for air, 32 to 36 Fr
or stab wounds in the vicinity of the diaphragm requires more
for pleural effusions, and 36 to 40 Fr for blood or pus). Small-
extensive evaluation before tube placement. In addition, co-
caliber Silastic tubes have been increasingly employed for chest
agulopathies should be corrected before tube insertion in a
drainage, particularly after open-heart surgery, to decrease pain
nonemergent setting. A clinical study showed that placement of
and encourage earlier ambulation [24].
chest tubes under emergency conditions (e.g., trauma) using the
Before performing the procedure, it is important to review
lateral approach results in more tube misplacements than us-
the steps to be taken and to ensure that all necessary equipment
ing the anterior approach. Although no clinical or functional
is available. Patient comfort and safety are paramount. There
consequences were observed after the misplaced tubes were
are three techniques for insertion of a thoracostomy tube. The
repositioned, the risk of malpositioning should be considered
first two direct techniques require a surgical incision and are
if the patient is obese, has large breasts, or has a clear history
(i) blunt dissection and (ii) trocar puncture. Only the former
of cardiomegaly [23].
technique has been discussed as the latter is not commonly
employed. The third technique is the percutaneous method,
which can also be done at the bedside with US guidance.
TECHNIQUE
1. With the patient supine and the head of the bed adjusted
Chest tube insertion requires knowledge not only of the for comfort, the involved side is elevated slightly with the
anatomy of the chest wall and intrathoracic and intra- ipsilateral arm brought up over the head (Fig. 8.1). Sup-
abdominal structures, but also of general aseptic technique. plemental oxygen is administered as needed. Localize the
The procedure should be performed or supervised only by expe- borders of the triangle of safety whenever possible (A: be-
rienced personnel, because the complications of an improperly low level of axillary vessels; B: above fifth intercostal space
placed tube may have immediate life-threatening results. Be- at the anterior border of the latissimus dorsi; C: lateral bor-
fore tube placement, the patient must be evaluated thoroughly der of pectoralis major) [25].
by physical examination and chest films to avoid insertion of 2. The tube is usually inserted through the fourth or fifth
the tube into a bulla or lung abscess, into the abdomen, or intercostal space in the anterior axillary line. An alternative
even into the wrong side. Particular care must be taken before entry site (for decompression of a pneumothorax) is the
and during the procedure to avoid intubation of the pulmonary second intercostal space in the midclavicular line, but for
parenchyma. cosmetic reasons and to avoid the thick pectoral muscles,
The necessary equipment is provided in Table 8.2. Sterile the former site is preferable in adults.
technique is mandatory whether the procedure is performed in 3. Under sterile conditions, the area is prepared with 2%
the operating room, in the intensive care unit, in the emergency chlorhexidine in 70% isopropyl alcohol, and after allow-
room, or on the ward. Detailed informed consent is obtained, ing it to dry, it is draped to include the nipple, which serves
and a time-out is performed to make sure all the equipment is as a landmark, as well as the axilla. A 2- to 3-cm area is
ready and available and that the procedure is being done on infiltrated with 1% lidocaine to raise a wheal two finger-
the correct side and correct patient. breadths below the intercostal space to be penetrated. (This
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86 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

FIGURE 8.1. Positioning of the patient with the arm flexed over the FIGURE 8.2. Dissection with Kelly clamp.
head. Identification of the triangle of safety.

allows for a subcutaneous tunnel to be developed, through 7. The closed clamp is carefully inserted through the parietal
which the tube will travel, and discourages air entry into pleura, hugging the superior portion of the lower rib to
the chest following removal of the tube.) prevent injury to the intercostal bundle of the rib above.
4. A 2-cm transverse incision is made at the wheal, and ad- The clamp is placed to a depth of less than 1 cm to prevent
ditional lidocaine is administered to infiltrate the tissues injury to the intrathoracic structures and is spread open
through which the tube will pass, including a generous approximately 2 cm.
area in the intercostal space (especially the periosteum of 8. A finger is inserted into the pleural space to explore the
the ribs above and below the targeted interspace). Care anatomy and confirm proper location and lack of pleural
should be taken to anesthetize the parietal pleura fully, as symphysis. Only easily disrupted adhesions should be bro-
it (unlike the visceral pleura) contains pain fibers. Each in- ken. Bluntly dissecting strong adhesions may tear the lung
jection of lidocaine should be preceded by aspiration of the and initiate bleeding.
syringe to prevent injection into the intercostal vessels. Up 9. The end of the chest tube is grasped with the clamp and
to 30 to 40 mL of 1% lidocaine may be needed to achieve guided with the finger through the tunnel into the pleu-
adequate local anesthesia. ral space. Once the tip of the tube is in the pleural space,
5. To confirm the location of air or fluid, a thoracentesis is the clamp is removed and the chest tube is advanced and
then performed at the proposed site of tube insertion. If air positioned apically for a pneumothorax and dependently
or fluid is not aspirated, the anatomy should be reassessed for fluid removal (Fig. 8.3A, B). All holes must be con-
and chest radiographs and CT scans reexamined before firmed to be within the pleural space. The use of undue
proceeding. pressure or force to insert the tube should be avoided
6. A short tunnel is created to the chosen intercostal space (Fig. 8.4A, B).
using Kelly clamps and the intercostal muscles are bluntly 10. The location of the tube should be confirmed by observing
divided (Fig. 8.2). the flow of air (seen as condensation within the tube) or

A B

FIGURE 8.3. A, B: The clamp penetrates the intercostal muscle. The end of the chest tube is grasped
with a Kelly clamp and guided with a finger through the chest incision. The clamp can be placed above
or bellow the tube.
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Chapter 8: Chest Tube Insertion and Care 87

A B

FIGURE 8.4. A, B: Advance the tube once the clamp has been removed.

fluid from the tube. It is then sutured to the skin securely


to prevent slippage (Fig. 8.5). A simple suture to anchor COMPLICATIONS
the tube can be used or a horizontal mattress suture can
be used to allow the hole to be tied closed when the tube Chest tube insertion may be accompanied by significant com-
is removed. An occlusive petrolatum gauze dressing is ap- plications. In one series, insertion and management of pleural
plied, and the tube is connected to a drainage apparatus tubes in patients with blunt chest trauma carried a 9% inci-
and securely taped to the dressing and to the patient. All dence of complications. Insertion alone is usually accompa-
connections between the patient and the drainage appara- nied by a 1% to 2% incidence of complications even when
tus must also be tight and securely taped. performed by experienced personnel [26] (Table 8.3). The use
of small-caliber, less rigid, Silastic drains has been found to be
safe and efficacious as the more rigid, conventional chest tubes
[27], and they allow both more mobility and earlier discharge
when used in open-heart surgery patients [28].

CHEST TUBE MANAGEMENT


AND CARE
While a chest tube is in place, the tube and drainage system
must be checked daily for adequate functioning. Most institu-
tions use a three-chambered system that contains a calibrated
collection trap for fluid, an underwater seal unit to allow es-
cape of air while maintaining negative pleural pressure, and

TA B L E 8 . 3
COMPLICATIONS OF CHEST TUBE INSERTION

Unintentional tube placement into vital structures


(lung, liver, spleen, etc.)
Bleeding
Reexpansion pulmonary edema
FIGURE 8.5. The tube is securely sutured to the skin with a 10 or Residual pneumothorax
20 silk suture. This suture is left long, wrapped around the tube, and Residual hemothorax
secured with tape. To seal the tunnel, the suture is tied when the tube Empyema
is pulled out.
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88 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

a suction regulator. Suction is routinely established at 15 to or both. For a pneumothorax, the drainage system is left on
20 cm water, controlled by the height of the column in the suction until the air leak stops. If an air leak persists, brief
suction regulator unit, and maintained as long as an air leak clamping of the chest tube can be performed to confirm that
is present. The drainage system is examined daily to ensure the leak is from the patient and not the system. If, after sev-
that appropriate levels are maintained in the underwater seal eral days, an air leak persists, placement of an additional tube
and suction regulator chambers. If suction is desired, bubbling may be indicated. When the leak has ceased for more than
should be noted in the suction regulator unit. Connections be- 24 to 48 hours (or if no fluctuation is seen in the underwa-
tween the chest tube and the drainage system should be tightly ter seal chamber), the drainage system is placed on water seal
fitted and securely taped. For continuous drainage, the chest by disconnecting the wall suction, followed by a chest film
tube and the tubing to the drainage system should remain free several hours later. If no pneumothorax is present and no air
of kinks, should not be left in a dependent position, and should leak appears in the system with coughing, deep breathing, and
never be clamped. If problems are encountered with repeti- reestablishment of suction, the tube can be removed. For fluid
tive kinking, a corrugated tubing splint can be used around collections, the tube can be removed when drainage is less
the chest tube to improve the resistance [29]. The tube can be than 200 cc per 24 hours or lesser [33], unless sclerotherapy is
milked and gently stripped, although with caution, as this may planned.
generate negative pressures of up to 1,500 mm Hg and can in- Tube removal is often preceded by oral or parenteral analge-
jure adjacent tissues [30]. Irrigation of the tube is discouraged. sia at an appropriate time interval [34]. The suture holding the
Dressing changes should be performed every 2 or 3 days and tube to the skin is cut. At end-inspiration, the tube is pulled out
as needed. Adequate pain control is mandatory to encourage and the hole simultaneously covered with occlusive petrolatum
coughing and ambulation to facilitate lung reexpansion. gauze dressing at peak inspiration or end expiration the chest
Chest films can be obtained to evaluate the progress of tube is pulled [35]. A chest radiograph is performed immedi-
drainage and to ensure that the most proximal drainage hole ately to check for a pneumothorax if there are clinical signs and
has not migrated from the pleural space (a situation that may symptoms or if the patient is at high risk for reaccumulation;
result in pneumothorax or subcutaneous emphysema). If this otherwise, a nonurgent chest radiograph can be ordered and
occurs and the pathologic process is not corrected, replacement repeated 24 hours later to rule out reaccumulation of air or
of the tube is usually indicated, especially if subcutaneous em- fluid [36].
physema is developing. Mandatory routine daily chest X-rays
are not indicated to monitor chest tubes in the intensive care
unit unless there is a clinical necessity [31]. A tube should never
be readvanced into the pleural space, and if a tube is to be re- RELATED SYSTEMS
placed, it should always be at a different site rather than the
same hole. If a pneumothorax persists, increasing the suction Percutaneous aspiration of the pleural space to relieve a pneu-
level may be beneficial, but an additional tube may be required mothorax without an active air leak has been reported. Al-
if no improvement results; other etiologies should be consid- though successful in up to 75% cases of needle-induced or
ered after this point and further evaluation with a CT scan of traumatic pneumothoraces, the success rate is less for
the chest. Proper positioning may also be confirmed by chest those with a spontaneous pneumothorax [37,38]. Small-bore
CT scanning [32]. catheters placed via Seldinger technique or using a trocar have
been successful for treatment of spontaneous and iatrogenic
pneumothoraces [3941].
CHEST TUBE REMOVAL Heimlich valves (one-way flutter valves that allow egress of
air from pleural tubes or catheters) have also gained popularity
Indications for removal of chest tubes include resolution of because ambulation is facilitated and outpatient care can be
the pneumothorax or fluid accumulation in the pleural space, provided to those with persistent air leaks [42,43].

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JAMA 155:24, 1954. 19. Cope C, Salem R, Kaiser LR: Management of chylothorax by percuta-
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9. Sandrasagra FA: Management of penetrating stab wounds of the chest: as- 20. Hausheer FH, Yarbro JW: Diagnosis and treatment of malignant pleural ef-
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10. McNamara JJ, Messersmith JK, Dunn RA, et al: Thoracic injuries in combat 21. Milanez RC, Vargas FS, Filomeno LB, et al: Intrapleural talc for the treatment
casualties in Vietnam. Ann Thorac Surg 10:389, 1970. of malignant pleural effusions secondary to breast cancer. Cancer 75:2688,
11. Boyd AD: Pneumothorax and hemothorax, in Hood RM, Boyd AD, Cul- 1995.
liford AT (eds): Thoracic Trauma. Philadelphia, PA, WB Saunders, 1989, 22. Heffner JE, Standerfer RJ, Torstveit J, et al: Clinical efficacy of doxycycline
p 133. for pleurodesis. Chest 105:1743, 1994.
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Chapter 9: Bronchoscopy 89

23. Kang SN: Rib fractures, pneumothorax, haemothorax and chest drain inser- 33. Younes RN, Gross JL, Aguiar S, et al: When to remove a chest tube? A
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CHAPTER 9 BRONCHOSCOPY
STEPHEN J. KRINZMAN, PAULO J. OLIVEIRA AND RICHARD S. IRWIN

Since its commercial introduction for clinical use in 1968, flex-


ible bronchoscopy has had a dramatic impact on the approach DIAGNOSTIC INDICATIONS
and management of patients with a wide variety of respira-
tory problems [1]. Because of its safety, low complication rate
[2], and comfort [3], flexible bronchoscopy has largely re- General Considerations
placed rigid bronchoscopy as the procedure of choice for most
endoscopic evaluations of the airway. However, rigid bron- Because flexible bronchoscopy can be performed easily even in
choscopy is indicated for (a) brisk hemoptysis (200 mL per intubated patients, the same general indications apply to crit-
24 hours); (b) extraction of foreign bodies; (c) endobronchial ically ill patients on ventilators and noncritically ill patients;
resection of granulation tissue that might occur after traumatic however, only the indications most commonly encountered in
and/or prolonged intubation; (d) biopsy of vascular tumors critically ill patients are discussed here. Where relevant, the po-
(e.g., bronchial carcinoid), in which brisk and excessive bleed- tential application of advanced bronchoscopic diagnostic and
ing can be controlled by packing; (e) endoscopic laser surgery; therapeutic interventions in the intensive care unit (ICU) setting
and (f) dilation of tracheobronchial strictures and placement are also discussed.
of airway stents [1,4]. In the last two decades, there has been
renewed interest in the use of rigid bronchoscopy by
pulmonologists, driven by the advent of dedicated endo- Common Indications
bronchial prostheses (airway stents) in the early 1990s and
the application of advanced bronchoscopic modalities (laser
photoresection, electrocautery, and cryotherapy) for the man- Hemoptysis
agement of both malignant and benign central airway ob- Hemoptysis is one of the most common clinical problems for
structions [5,6]. These advances in bronchoscopy have fused which bronchoscopy is indicated [8,9] (see Chapter 53 for a
older techniques and instruments, such as rigid bronchoscopy, detailed discussion). Whether the patient complains of blood
with novel applications of flexible bronchoscopy, spurring streaking or massive hemoptysis (expectoration of greater than
the development of the field of interventional pulmonology. 600 mL in 48 hours), bronchoscopy should be considered to
In an attempt to establish uniformity in the training and localize the site of bleeding and diagnose the cause. Localiza-
performance of bronchoscopy and advanced interventions, tion of the site of bleeding is crucial if definitive therapy, such
the American College of Chest Physicians recently pub- as surgery, becomes necessary, and it is also useful to guide
lished comprehensive guidelines for interventional pulmonary angiographic procedures. Bronchoscopy performed within
procedures [7]. 48 hours of the time when bleeding stops is more likely to
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90 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

localize the site of bleeding (34% to 91%) compared with 50% of all significant bacterial species initially identified in
delayed bronchoscopy (11% to 52%) [10]. Bronchoscopy is significant numbers had colony counts reduced to below the
more likely to identify a bleeding source in patients with mod- pathogenic threshold level. After 48 hours of therapy, only
erate or severe hemoptysis [11]. Whenever patients have an en- 14% of isolates are still present above threshold values [22].
dotracheal or tracheostomy tube in place, hemoptysis should It is therefore essential to obtain quantitative cultures before
always be evaluated, because it may indicate potentially life- starting or changing antibiotics.
threatening tracheal damage. Unless the bleeding is massive, a Despite the greater accuracy of quantitative bronchoscopic
flexible bronchoscope, rather than a rigid bronchoscope, is the cultures, prospective randomized trials of early invasive di-
instrument of choice for evaluating hemoptysis. In the setting agnostic strategies employing bronchoscopy and quantitative
of massive hemoptysis, the patient is at risk for imminent de- lower respiratory tract cultures for VAP have not demonstrated
compensation and death due to asphyxiation. Stabilization of significant advantages in mortality or other major clinical end
the patient, focusing on establishment of a secure airway, and points [23,24] over simpler methods. The largest such trial
timely communication with pulmonology, thoracic surgery, [24] found that compared to therapy based on nonquantitative
anesthesiology, and interventional radiology is of utmost im- endotracheal aspirates, patients randomized to bronchoscopy
portance. This coordinated, multidisciplinary effort should fo- with quantitative cultures had no improvement in mortality,
cus on rapid transfer to the operation room (OR) suite for rigid duration of mechanical ventilation, or length of ICU or hospital
bronchoscopy. The rigid bronchoscope is ideal in this situation stay. On the basis of these findings, routine use of bronchoscopy
because it provides a secure route for ventilation, serves as a in immunocompetent adults with suspected VAP cannot be rec-
larger conduit for adequate suctioning, and can quickly isolate ommended.
the lung in the case of a lateralized bleeding source. In most
situations, once an adequate airway has been established and Pulmonary Infiltrates in Immunocompromised Patients
initial suctioning of excessive blood has been performed, the
When an infectious process is suspected, the diagnostic yield
flexible bronchoscope can be inserted through the rigid bron-
depends on the organism and the immune status of the pa-
choscope to more accurately assess and localize the source of
tient. In immunocompetent patients, BAL has a sensitivity of
bleeding beyond the main bronchi [12].
87% for detecting respiratory pathogens [19], and a negative
BAL quantitative culture has a specificity of 96% in predicting
Diffuse Parenchymal Disease sterile lung parenchyma. Numerous recent investigations have
The clinical setting influences the choice of procedure. When examined the utility of bronchoscopy in immunocompromised
diffuse pulmonary infiltrates suggest sarcoidosis, carcinomato- patients. Most of these investigations have found that the diag-
sis, or eosinophilic pneumonia, transbronchoscopic lung for- nostic yield of BAL in such patients is approximately 50% and
ceps biopsy should be considered initially because it has an that the results of BAL lead to a change in treatment in 17%
extremely high yield in these situations (see Chapter 69). Trans- to 38% of patients. In one prospective multicenter trial [25],
bronchial lung biopsy has a low yield for the definitive diag- BAL was the only conclusive diagnostic study in 33% of pa-
nosis of inorganic pneumoconiosis and pulmonary vasculitides tients. Although it is difficult to distinguish respiratory decom-
[13]; when these disorders are suspected, surgical lung biopsy pensation caused by bronchoscopy from the natural history
is the procedure of choice. In the case of pulmonary fibrosis of the patients underlying disease, the same study found that
and acute interstitial pneumonitis, transbronchial biopsy usu- 48% of patients developed deterioration in respiratory status
ally does not provide adequate tissue for a specific histologic after bronchoscopy and 27% of patients were intubated. Trans-
diagnosis, although by excluding infection the procedure may bronchial biopsy may add little to the diagnostic yield of BAL
provide sufficient information to guide therapy. in immunocompromised patients, with an incremental yield of
7% to 12% [2629]. In some series, the major complication
Ventilator-Associated Pneumonia rate of transbronchial biopsy was greater than the diagnostic
utility, including a 14% incidence of major bleeding requir-
The ability to determine the probability of ventilator-associated
ing intubation [29]. BAL has a relatively poor sensitivity for
pneumonia (VAP) is very limited, with a sensitivity of only
detecting fungal infections in this population (40%) [26]. In
50% and a specificity of 58% [14]. Quantitative cultures ob-
AIDS patients, the sensitivity of lavage or transbronchial lung
tained via bronchoscopy may thus play an important role in
biopsy for identifying all opportunistic organisms can be as
the diagnostic strategy. Quantitative cultures of bronchoalve-
high as 87% [30,31]. Transbronchial biopsy adds significantly
olar lavage (BAL) fluid and protected specimen brush (PSB),
to the diagnostic yield in AIDS patients and may be the sole
with thresholds of 104 colony-forming units (CFU) per mL
means of making a diagnosis in up to 24% of patients, includ-
and 103 CFU per mL, respectively, are most commonly em-
ing diagnoses of Pneumocystis jirovecii, Cryptococcus neofor-
ployed prior to initiation of antimicrobial therapy. Cultures of
mans, Mycobacterium tuberculosis, and nonspecific interstitial
bronchial washings do not add to the diagnostic yield of quan-
pneumonitis [32]. Lavage alone may have a sensitivity of up to
titative BAL culture alone [15]. For a brief description of how
97% for the diagnosis of P. jirovecii pneumonia [33]. How-
to perform BAL and obtain PSB cultures, see the Procedure
ever, because induced sputum samples can also be positive for
section, given later in the chapter.
P. jirovecii in up to 79% of cases [33], induced expectorated
For BAL, an evidence-based analysis of 23 prior investi-
sputum, when available, should be evaluated first for this or-
gations yields a sensitivity of 73% and a specificity of 82%,
ganism before resorting to bronchoscopy.
indicating that BAL cultures fail to diagnose VAP in almost
one-fourth of all cases [16]. A similar analysis of PSB cultures
indicates a very wide range of results, with a sensitivity of 33%
Acute Inhalation Injury
to greater than 95% and a median of 67%, and a specificity In patients exposed to smoke inhalation, flexible nasopharyn-
of 50% to 100% with a median of 95% [17,18]. PSB is thus goscopy, laryngoscopy, and bronchoscopy are indicated to
more specific than it is sensitive, and negative results may not identify the anatomic level and severity of injury. Prophylactic
be sufficient to exclude the presence of VAP [19]. Blind pro- intubation should be considered if considerable upper airway
tected telescoping catheter specimens yield similar results to mucosal injury is noted early; acute respiratory failure is more
bronchoscopically directed PSB cultures [20,21]. It is critical likely in patients with mucosal changes seen at segmental or
to note that colony counts change very quickly with antibi- lower levels [34]. Upper airway obstruction is a life-threatening
otic therapy. Within 12 hours of starting antibiotic therapy, problem that usually develops during the initial 24 hours
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Chapter 9: Bronchoscopy 91

after inhalation injury. It correlates significantly with increased with asthma, these patients must be pretreated with a bron-
size of cutaneous burns, burns of the face and neck, and rapid chodilator.
intravenous fluid administration, and also portends a greater
mortality [35].
Foreign Bodies
Blunt Chest Trauma
Patients may present with atelectasis, pulmonary contusion, Although the rigid bronchoscope is considered by many to be
hemothorax, pneumothorax, pneumomediastinum, or hemop- the instrument of choice for removing foreign bodies, devices
tysis. Prompt bronchoscopic evaluation of such patients has with which to grasp objects are available for use with the flexi-
a diagnostic yield of 53%; findings may include tracheal or ble bronchoscope [41]. A review of flexible bronchoscopy in the
bronchial laceration or transection (14%), aspirated material management of tracheobronchial foreign bodies in adults from
(6%), supraglottic tear with glottic obstruction (2%), mucus the Mayo Clinic demonstrated a success rate of 89% [42]. The
plugging (15%), and distal hemorrhage (13%) [36]. Many of success of flexible bronchoscopy in foreign body removal can
these diagnoses may not be clinically evident and require sur- be enhanced by rigorous preprocedure preparation, assuring
gical intervention. the availability of appropriate ancillary grasping equipment,
practicing a dry run, and ensuring that a bronchoscopist
with experience in foreign body removal is involved. It is also
Postresectional Surgery important to have an appreciation for situations in which rigid
Flexible bronchoscopy can identify a disrupted suture line bronchoscopy with added ancillary interventions, such as laser
causing bleeding and pneumothorax following surgery and an therapy or cryotherapy, might be useful (e.g., an embedded for-
exposed endobronchial suture causing cough. In these postp- eign body with significant granulation tissue reaction at risk for
neumonectomy situations, the location of dehiscence and the bleeding) [43].
subsequent bronchopleural fistula (BPF) is easily identified vi-
sually via flexible bronchoscopy at the stump site. However,
when the BPF occurs in the setting of acute respiratory distress
syndrome (ARDS) or necrotizing pneumonia, localization at
Endotracheal Intubation
the segmental and subsegmental level can be more challenging. In patients with ankylosing spondylitis and other mechanical
Readers are referred to Chapter 57, which comprehensively problems of the neck, the flexible bronchoscope may be used
covers this topic. as an obturator for endotracheal intubation. The broncho-
scope with an endotracheal tube passed over it can be passed
Assessment of Intubation Damage transnasally (after proper local anesthesia) or transorally. The
tube can then be advanced over the scope.
When a nasotracheal or orotracheal tube of the proper size is in
place, the balloon can be routinely deflated and the tube with-
drawn over the bronchoscope to look for subglottic damage.
The tube is withdrawn up through the vocal cords and over Hemoptysis
the flexible bronchoscope and glottic and supraglottic damage
sought. This technique may by useful after reintubation for stri- On rare occasions where brisk bleeding threatens asphyxia-
dor, or when deflation of the endotracheal tube cuff does not tion, endobronchial tamponade may stabilize the patient be-
produce a significant air leak, suggesting the potential for life- fore definitive therapy is performed (see Chapter 53). With
threatening upper airway obstruction when extubation takes the use of the flexible bronchoscope, usually passed through
place. The flexible bronchoscope may readily identify mechan- a rigid bronchoscope or endotracheal tube, a Fogarty catheter
ical problems such as increased airway granulation tissue lead- with balloon is passed into the bleeding lobar orifice. When the
ing to airway obstruction, tracheal stenosis at pressure points balloon is inflated and wedged tightly, the patient may be trans-
along the artificial airwaytracheal interface, and tracheobron- ferred to surgery or angiography for bronchial arteriography
chomalacia. and bronchial artery embolization [44]. Other bronchial block-
ing and lung separation techniques have been described and
reviewed in the literature [45]. The wire-guided endobronchial
blocker (Arndt blocker) is a dedicated bronchial blocker that
THERAPEUTIC INDICATIONS has a wire loop at its distal end, whichwhen looped around
the distal end of the flexible bronchoscopecan be guided to
Atelectasis the bleeding airway, inflated, and its position adjusted under
direct visualization. More simple techniques that take advan-
When atelectasis occurs in critically ill patients who had a tage of the flexible bronchoscopes ability to act as a stylet for
normal chest film on admission, mucus plugging is the most a single-lumen endotracheal tube can be used to separate the
likely cause [37]. Bronchoscopy has a success rate of up to lung. One can use the bronchoscope to preferentially intubate
89% in cases of lobar atelectasis, but only produced clini- the right main or left main bronchus in an acute, emergent
cal improvement in 44% of patients when performed for re- situation. Hemostasis may also be achieved by using flexible
tained secretions [38]. One randomized trial found no ad- bronchoscopy to apply oxidized regenerated cellulose mesh to
vantage of bronchoscopy over a very aggressive regimen of the bleeding site, instill thrombin/thrombinfibrinogen prepa-
frequent chest physiotherapy, recruitment maneuvers, saline rations, and more traditionally, perform iced saline lavage or
nebulization, and postural drainage [39]. This study also found apply topical epinephrine (1:20,000) to temporize the bleeding
that the presence of air bronchograms on the initial chest [10,46]. There have also been reports of treating hemoptysis
X-ray predicted relative failure of either intervention to resolve by instilling cyanoacrylate through a catheter in the working
the atelectasis. Occasionally, the direct instillation of acetyl- channel of the flexible bronchoscope [47]. In the case of a visi-
cysteine (Mucomyst) through the bronchoscope may be nec- bly bleeding endobronchial tumor, hemostasis can be attained
essary to liquefy the thick, tenacious inspissated mucus [40]. with laser photocoagulation (Nd-YAG laser), electrocautery,
Because acetylcysteine may induce bronchospasm in patients or argon plasma coagulation.
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92 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

often occur (15.4% to 33%) after rigid bronchoscopy [63],


Central Obstructing Airway Lesions probably due to trauma to the teeth and airways. Most in-
vestigations have found that the incidence of bacteremia after
Some patients with cancer and others with benign lesions that transoral flexible bronchoscopy is much lower (0.7%) [64].
obstruct the larynx, trachea, and major bronchi can be treated Current guidelines by the American Heart Association for res-
by electrocautery, laser photoresection, argon plasma coagula- piratory tract procedures recommend prophylactic antibiotics
tion, cryotherapy, or photodynamic therapy applied through only when incision or biopsy of the respiratory tract mucosa
the bronchoscope (rigid or flexible) [4855]. Flexible bron- is anticipated. Prophylaxis is further restricted to patients with
choscopy can also be used to place catheters that facilitate high-risk cardiac conditions (prosthetic valves, prior history
endobronchial delivery of radiation (brachytherapy). Metal or of infective endocarditis, congenital heart disease, and cardiac
silicone endobronchial stents can be placed bronchoscopically transplantation with valvulopathy) only and no distinction is
to relieve stenosis of large central airways. Adequate insertion made between rigid and flexible bronchoscopy [65].
of stents and relief of stenosis (especially due to extrinsic com- Although routine bronchoscopy is extremely safe, critically
pression) is typically accompanied by dilation of the airway ill patients appear to be at higher risk of complications. Patients
via rigid bronchoscopy or with balloon dilation applied with with asthma are prone to develop laryngospasm and bron-
the aid of flexible bronchoscopy. Several issues regarding air- chospasm. Bone marrow and stem cell transplant recipients are
way stents should be noted: silicone stents can only be placed more likely to develop major bleeding during bronchoscopy
via rigid bronchoscopy and metal stents should generally not (0% to 14%) [28,66], particularly if PSB or transbronchial
be used in the setting of a nonmalignant central airway ob- lung biopsy is performed (7% to 14% vs. 1.5% for BAL alone)
struction because they are associated with excessive growth [29,66]. Patients with uremia are at increased risk of bleeding
of granulation tissue with subsequent worsening of airway [67]. One investigation found that aspirin use did not increase
obstruction and can be very challenging to remove once this bleeding risk after transbronchial biopsy [68]. In critically ill,
complication occurs [51]. The primary goal of the interven- mechanically ventilated patents, bronchoscopy causes a tran-
tions described earlier for the management of malignant cen- sient decrease in PaO2 (partial arterial oxygen pressure) of ap-
tral airway obstruction is palliative. Multiple case reports have proximately 25% [69], and transbronchial lung biopsy is more
confirmed that these interventions improve quality of life by likely to result in pneumothorax (7% to 23%) [70], particu-
relieving symptoms of dyspnea almost immediately [5255]. larly in patients with ARDS (up to 36%) [71]. Patients with
In many instances, these procedures also facilitate liberation ARDS also have more pronounced declines in oxygenation,
from mechanical ventilation and downgrading of the level of with a mean decrease of more than 50% in the PaO2 [69].
care from the ICU. It appears that in intubated ICU patients,
flexible bronchoscopy performed at the bedside with stent de-
ployment and resective interventions, when necessary, is just as
effective as rigid bronchoscopic interventions in the appropri-
ately selected patient [54].
CONTRAINDICATIONS
Bronchoscopy should not be performed (a) unless an experi-
enced bronchoscopist is available; (b) when the patient will not
Closure of Bronchopleural Fistula or cannot cooperate; (c) when adequate oxygenation cannot be
maintained during the procedure; (d) in unstable cardiac pa-
After placement of a chest tube, drainage of the pleural space, tients [7274]; and (e) in untreated symptomatic patients with
and stabilization of the patient (e.g., infection and cardiovas- asthma [75]. The impact of coagulation parameters and an-
cular and respiratory systems), bronchoscopy can be used to tiplatelet agents on bleeding risk during transbronchial biopsy
visualize a proximal BPF or localize a distal BPF; it can also be remains controversial [68,76]. In patients with recent cardiac
used in attempts to close the BPF [56]. Please see Chapter 57, ischemia, the major complication rate is low (3% to 5%) and
which comprehensively covers this topic. is similar to that of other critically ill populations [77,78]. Al-
though patients with stable carbon dioxide retention can safely
undergo bronchoscopy with a flexible instrument [79], premed-
Percutaneous Dilatational Tracheostomy ication, sedation during the procedure, and supplemental oxy-
gen must be used with caution. The major contraindications to
Flexible bronchoscopic guidance is extremely helpful during rigid bronchoscopy include inability to tolerate general anes-
bedside percutaneous tracheostomy [57,58]. Please see Chapter thesia, an unstable cervical spine, limited range of motion at
12, which comprehensively covers this topic. the spine, any condition that inhibits opening of the jaw, and
an inexperienced operator and staff [5].
Consideration of bronchoscopy in neurologic and neurosur-
COMPLICATIONS gical patients requires attention to the effects of bronchoscopy
on intracranial pressure (ICP) and cerebral perfusion pressure
When performed by a trained specialist, routine flexible bron- (CPP). In patients with head trauma, bronchoscopy causes the
choscopy is extremely safe. Mortality should not exceed 0.1%, ICP to increase by at least 50% in 88% of patients and by at
and overall complications should not exceed 8.1% [2]. The rare least 100% in 69% of patients despite the use of deep sedation
deaths have been due to excessive premedication or topical and paralysis [80]. Because mean arterial pressure tends to rise
anesthesia, respiratory arrest from hemorrhage, laryngospasm in parallel with ICP, there is often no change in CPP. No signifi-
or bronchospasm, and cardiac arrest from acute myocardial cant neurologic complications have been noted in patients with
infarction [59,60]. Nonfatal complications occurring within severe head trauma [80,81] or with space-occupying intracra-
24 hours of the procedure include fever (1.2% to 24%) [2,61], nial lesions with computed tomographic evidence of elevated
pneumonia (0.6% to 6%) [2], vasovagal reactions (2.4%) [2], ICP [82]. Bronchoscopy in such patients should be accompa-
laryngospasm or bronchospasm (0.1% to 0.4%) [2], cardiac nied by deep sedation, paralysis, and medications for cerebral
arrhythmias (0.9% to 4%) [2,62], pneumothorax, anesthesia- protection (thiopental and lidocaine). Cerebral hemodynam-
related problems (0.1%) [2], and aphonia (0.1%) [2]. Fever ics should be continuously monitored to ensure that ICP and
may occur in up to 24% of patients after bronchoscopy and CPP are within acceptable levels. Caution is warranted in pa-
appears to be cytokine mediated and uncommonly indicative tients with markedly elevated baseline ICP or with borderline
of a true infection or bacteremia [61]. Transient bacteremias CPP.
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Chapter 9: Bronchoscopy 93

dose without improving cough or patient comfort [94]. Mod-


PROCEDURE erate sedation with incremental doses of midazolam, titrated
to produce light sleep, produces amnesia in more than 95% of
patients, but adequate sedation may require a total of greater
Airway and Intubation than 20 mg in some subjects [95]. Cough suppression is more
In nonintubated patients, flexible bronchoscopy can be per- effective when narcotics are added to benzodiazepine premedi-
formed by the transnasal or transoral route with a bite block cation regimens [95]. Premedication with intravenous atropine
[1]. There has also been a relatively recent interest in perform- has not been found to reduce secretions, decrease coughing,
ing noninvasive ventilation-assisted flexible bronchoscopy via or prevent bradycardia [96,97] and has been associated with
face mask, first described in eight immunocompromised pa- greater hemodynamic fluctuations when compared to placebo
tients with infiltrates and severe hypoxemia (PaO2 /FIO2 <100) [98]. Propofol [99] and fospropofol [100] have also been used
[83]. The procedure was well tolerated with either maintenance with success during moderate sedation for bronchoscopy, and
of or an improvement in oxygenation noted throughout, and may have the advantage of more rapid onset and shorter re-
none of the patients required intubation. Since then, multi- covery time.
ple case reports and small randomized controlled trials using
similar applications of noninvasive ventilation during bron-
choscopy in expanded patient populations with severe hypox- Mechanical Ventilation
emia (PaO2 /FIO2 <200) have been described with similar out-
comes [84,85]. Thus, it appears that this technique, augmented Maintaining adequate oxygenation and ventilation while pre-
by BAL, appears to be a safe, effective, and viable option of ob- venting breath stacking and positive end expiratory pressure
taining an early and accurate diagnosis of pneumonia in nonin- (auto-PEEP) may be challenging when insertion of the bron-
tubated, otherwise marginal, patients with severe hypoxemia. choscope reduces the effective lumen of the endotracheal tube
In intubated and mechanically ventilated patients, the flexible by more than 50%. PEEP caused by standard scopes and tubes
bronchoscope can be passed into the tube through a swivel will approach 20 cm H2 O with the potential for barotrauma
adapter with a rubber diaphragm that will prevent loss of the [87]. The inspired oxygen concentration must be temporarily
delivered respiratory gases [86]. To prevent dramatic increases increased to 100% prior to starting the procedure [87]. Expired
in airway resistance and an unacceptable loss of tidal volumes, volumes should be constantly monitored to ensure that they are
the lumen of the endotracheal tube should be at least 2 mm adequate [88]. Meeting these ventilatory goals may require in-
larger than the outer diameter of the bronchoscope [87,88]. creasing the high-pressure limit in volume-cycled ventilation
Thus, flexible bronchoscopy with an average adult-sized in- to near its maximal value, allowing the ventilator to overcome
strument (outside diameter of scope 4.8 to 5.9 mm) can be the added resistance caused by the bronchoscope. Although
performed in a ventilated patient if there is an endotracheal this increases the measured peak airway pressure, the alveolar
tube in place that is 8 mm or larger in internal diameter. If the pressure is not likely to change significantly because the lung
endotracheal tube is smaller, a pediatric bronchoscope (outside is protected by the resistance of the bronchoscope [88]. Alter-
diameter 3.5 mm) or intubation endoscope (outside diameter natively, decreasing the inspiratory flow rate in an attempt to
3.8 mm) must be used. Both diagnostic and therapeutic inter- decrease measured peak pressures may paradoxically increase
ventions via flexible bronchoscopy have also been performed alveolar pressures by decreasing expiratory time and thus in-
more frequently in the last decade through laryngeal mask air- creasing auto-PEEP. Suctioning should be kept to a minimum
ways used to secure the airway in spontaneously breathing and and for short periods of time because it will decrease the tidal
generally anesthetized individuals [89]. volumes being delivered [87].

Premedication Quantitative Cultures


Topical anesthesia may be achieved by hand-nebulized lido- BAL is performed by advancing the bronchoscope until the tip
caine and lidocaine jelly as a lubricant [1] and by instilling wedges tightly in a distal bronchus from the area of greatest
approximately 3 mL of 1% or 2% lidocaine at the main carina clinical interest. If the disease process is diffuse, perform the
and, if needed, into the lower airways. Lidocaine is absorbed procedure in the right middle lobe because this is the area from
through the mucus membranes, producing peak serum concen- which the best returns are most consistently obtained. Three
trations that are nearly as high as that when the equivalent dose aliquots of saline, typically 35 to 50 mL, are then instilled and
is administered intravenously, although toxicity is rare if the to- withdrawn; in some protocols, the first aliquot is discarded to
tal dose does not exceed 6 to 7 mg per kg. In 2000, a study prevent contamination with more proximal secretions. A total
performed in otherwise healthy patients with asthma demon- instilled volume of 100 mL with at least 5% to 10% retrieved
strated the safety of topical lidocaine doses up to 8.2 mg per kg constitutes an adequate specimen [101]. PSB may be performed
in this population [90] and subsequently led to this upper limit through a bronchoscope by advancing the plugged catheter
being recommended by the British Thoracic Society in their assembly until it projects from the bronchoscope. When the
guidelines for diagnostic flexible bronchoscopy [91]. In pa- area of interest is reached (e.g., purulent secretions can be seen),
tients with hepatic or cardiac insufficiency, lidocaine clearance the distal plug is ejected and the brush is then fully advanced
is reduced, and the dose should be decreased to a maximum beyond the protective sheath. After the specimen is obtained,
of 4 to 5 mg per kg [92,93]. Administering nebulized lidocaine the brush is pulled back into the sheath and only then is the
prior to the procedure substantially increases the total lidocaine catheter assembly removed from the bronchoscope.

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P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 10: Thoracentesis 95

78. Dunagan DP, Burke HL, Aquino SL, et al: Fiberoptic bronchoscopy in coro- 90. Langmack EL, Martin RJ, Pak J, et al: Serum lidocaine concentration
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79. Salisbury BG, Metzger LF, Altose MD, et al: Effect of fiberoptic bron- 91. Honeybourne D, Jabb J, Bowie P, et al: British Thoracic Society guidelines
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and clinical applications. J Bronchol 14:181188, 2007. Clin Chest Med 25:637, 2004.

CHAPTER 10 THORACENTESIS
MARK M. WILSON AND RICHARD S. IRWIN

Thoracentesis is an invasive procedure that involves the intro- uation of a pleural effusion of unknown etiology is presented
duction of a needle, cannula, or trocar into the pleural space to in Figure 10.1. In patients whose pleural effusion remains un-
remove accumulated fluid or air. Although a few prospective diagnosed after thoracentesis and closed pleural biopsy, tho-
studies have critically evaluated the clinical value and compli- racoscopy should be considered for visualization of the pleura
cations associated with it [13], most studies concerning tho- and directed biopsy. Thoracoscopy has provided a positive di-
racentesis have dealt with the interpretation of the pleural fluid agnosis in more than 80% of patients with recurrent pleural ef-
analyses [4,5]. fusions that are not diagnosed by repeated thoracentesis, pleu-
ral biopsy, or bronchoscopy.
Therapeutic thoracentesis is indicated to remove fluid or
air that is causing cardiopulmonary embarrassment or to re-
INDICATIONS lieve severe symptoms. Definitive drainage of the pleural space
with a thoracostomy tube must be done for a tension pneu-
Although history (cough, dyspnea, or pleuritic chest pain)
mothorax (PTX) and should be considered for a PTX that is
and physical findings (dullness to percussion, decreased breath
slowly enlarging, any size PTX in the mechanically ventilated
sounds, and decreased vocal fremitus) suggest that an effusion
patient, hemothorax, or the instillation of a sclerosing agent
is present, chest radiography or ultrasonic examination is es-
after drainage of a recurrent malignant pleural effusion.
sential to confirm the clinical suspicion. Thoracentesis can be
performed for diagnostic or therapeutic reasons. When done
for diagnostic reasons, the procedure should be performed
whenever possible before any treatment has been given to CONTRAINDICATIONS
avoid confusion in interpretation [5]. Analysis of pleural fluid
has been shown to yield clinically useful information in more Absolute contraindications to performing a thoracentesis are
than 90% of cases [2]. The four most common diagnoses for an uncooperative patient, the inability to identify the top of
symptomatic and asymptomatic pleural effusions are malig- the rib clearly under the percutaneous puncture site, a lack
nancy, congestive heart failure, parapneumonia, and postop- of expertise in performing the procedure, and the presence of
erative sympathetic effusions. A diagnostic algorithm for eval- a coagulation abnormality that cannot be corrected. Relative
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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96 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

Pleural Effusion(s)

Secure or Uncomplicated Dx Uncertain Dx or Atypical Features


CHF
Postoperative
Postpartum Lateral Decubitus Film

Small or Loculated >1 cm Free-Flowing Layer


Observe

Ultrasound

Thoracentesis

Diagnostic for: Exudate Transudate


Malignancy
Infection
Pancreatic Evaluate for:
Process or CHF
Esophageal Cirrhosis
Rupture Nephrotic Syndrome
Pulmonary Embolus

Nondiagnostic Repeat Thoracentesis Malignancy


and Closed Pleural Biopsy Granuloma

Evaluate and Treat for: Nonspecific Pleuritis Observe


Other Systemic Disease or Normal
Collagen Vascular Disease
Pulmonary Embolus
Subdiaphragmatic Disease
Unsuspected Chest Disease

Repeat Thoracentesis Malignancy


and Closed Pleural Biopsy Granuloma
or
Thoracoscopy with Biopsy

Observe Asbestos Nonspecific Pleuritis


Exposure

Uremia Stable Unstable FIGURE 10.1. Diagnostic algorithm for evaluation of


pleural effusion. CHF, congestive heart failure; Dx, diag-
nosis. [Adapted from Smyrnios NA, Jederlinic PJ, Irwin
RS: Pleural effusion in an asymptomatic patient. Spec-
Dialysis Observe Open Pleural trum and frequency of causes and management consid-
Biopsy erations. Chest 97:192, 1990.]

contraindications to a thoracentesis include entry into an area The reported incidence of PTX varies between 3% and 30%
where known bullous lung disease exists, a patient who is on [13,6,7], with up to one-third to one-half of those with
positive end-expiratory pressure, and a patient who has only demonstrated PTX requiring subsequent intervention. Various
one functioning lung (the other having been surgically re- investigators have reported associations between PTX and un-
moved or that has severe disease limiting its gas exchange func- derlying lung disease (chronic obstructive pulmonary disease,
tion). In these settings, it may be safest to perform the thora- prior thoracic radiation, prior thoracic surgery, or lung can-
centesis under ultrasonic guidance. cer) [8,9], needle size and technique [3,8], number of passes
required to obtain a sample [8], aspiration of air during the
procedure, experience level of the operator [1,3,6], use of a vac-
COMPLICATIONS uum bottle [9], size of the effusion [2,8], and mechanical ven-
tilation versus spontaneously breathing patients. Some of the
A number of prospective studies have documented that compli- above-mentioned studies report directly contradictory findings
cations associated with the procedure are not infrequent [1,2]. compared to other similar studies. This is most apparent in the
The overall complication rate has been reported to be as high reported association between PTX and therapeutic thoracente-
as 50% to 78%, and can be further categorized as major (15% sis [3,8], which was not supported by subsequent large prospec-
to 19%) or minor (31% to 63%) [2,3]. Complication rates tive trials [8,9]. The most likely explanation for this discrep-
appear to be inversely related to experience level of the oper- ancy in the literature concerning the presumed increased risk
ator; the more experienced, the fewer the complications [6]. for PTX for therapeutic over diagnostic procedures is the gen-
Although death due to the procedure is infrequently reported, erally lower experience level of the operator in the first group.
complications may be life threatening [1]. Small sample sizes also limit the generalization of reported find-
Major complications include PTX, hemopneumothorax, ings to allow for the delineation of a clear risk profile for the
hemorrhage, hypotension, and reexpansion pulmonary edema. development of a PTX due to thoracentesis. The presence of
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 10: Thoracentesis 97

baseline lung disease, low experience level of the operator with receive appropriate supervision from an experienced oper-
the procedure, and the use of positive-pressure mechanical ven- ator before performing thoracentesis on their own.
tilation appear for now to be the best-established risk factors 3. With the patient sitting, arms at sides, mark the inferior tip
in the literature. Further research involving more patients is of the scapula on the side to be tapped. This approximates
needed. the eighth intercostal space and should be the lowest inter-
Although PTX is most commonly due to laceration of lung space punctured, unless it has been previously determined
parenchyma, room air may enter the pleural space if the tho- by sonography that a lower interspace can be safely entered
racentesis needle is open to room air when a spontaneously or chest radiographs and sonography show the diaphragm
breathing patient takes a deep breath. (Intrapleural pressure is to be higher than the eighth intercostal space.
subatmospheric.) The PTX may be small and asymptomatic, 4. Position the patient sitting at the edge of the bed, com-
resolving spontaneously, or large and associated with respira- fortably leaning forward over a pillow-draped, height-
tory compromise, requiring chest tube drainage. Hemorrhage adjusted, bedside table (Fig. 10.2). The patients arms
can occur from laceration of an intercostal artery or inadvertent should be crossed in front to elevate and spread the scapu-
puncture of the liver or spleen even if coagulation studies are lae. An assistant should stand in front of the patient to
normal. The risk of intercostal artery laceration is greatest in prevent any unexpected movements.
the elderly because of increased tortuosity of their vessels. This 5. Percuss the patients posterior chest to determine the high-
last complication is potentially lethal, and open thoracotomy est point of the effusion. The interspace below this point
may be required to control the bleeding. should be entered in the posterior axillary line, unless it is
Hypotension may occur during the procedure (as part of a below the eighth intercostal space. Gently mark the supe-
vasovagal reaction or tension PTX) or hours after the proce- rior aspect of the rib in the chosen interspace with your
dure (most likely due to reaccumulation of fluid into the pleu- fingernail. (The inferior portion of each rib contains an
ral space or the pulmonary parenchyma from the intravascular intercostal artery and should be avoided.)
space). Hypotension in the latter settings responds to volume 6. Cleanse the area with 2% chlorhexidine in 70% isopropyl
expansion; it can usually be prevented by limiting pleural fluid alcohol and allow it to dry. Using sterile technique, drape
drainage to 1.5 L or less. Other major complications are rare, the area surrounding the puncture site.
and include implantation of tumor along the needle tract of 7. Anesthetize the superficial skin with 2% lidocaine using a
a previously performed thoracentesis, venous and cerebral air 25-gauge needle. Change to an 18- to 22-gauge, 2-in.-long
embolism (so-called pleural shock) [10,11], and inadvertent needle and generously anesthetize the deeper soft tissues,
placement of a sheared-off catheter into the pleural space [1]. aiming for the top of the rib. Always aspirate through the
Minor complications include dry tap or insufficient fluid, syringe as the needle is advanced and before instilling li-
pain, subcutaneous hematoma or seroma, anxiety, dyspnea, docaine to ensure that the needle is not in a vessel or the
and cough [2]. Reported rates for these minor complications pleural space. Carefully aspirate through the syringe as the
range from 16% to 63% and depend on the method used to pleura is approached. (The rib is 1 to 2 cm thick.) Fluid
perform the procedure, with higher rates associated with the enters the syringe on reaching the pleural space. The pa-
catheter-through-needle technique [2,3]. Dry tap and insuffi- tient may experience discomfort as the needle penetrates
cient fluid are technical problems, and they expose the pa- the well-innervated parietal pleura. Be careful not to instill
tient to increased risk of morbidity because of the need to anesthetic into the pleural space; it is bactericidal for most
perform a repeat thoracentesis. Under these circumstances, it organisms, including Mycobacterium tuberculosis. Place
is recommended that the procedure be repeated under direct a gloved finger at the point on the needle where it exits
sonographic guidance. Pain may originate from parietal pleu- the skin (to estimate the required depth of insertion) and
ral nerve endings from inadequate local anesthesia, inadvertent remove the needle.
scraping of rib periosteum, or piercing an intercostal nerve dur- 8. Attach a three-way stopcock to a 20-gauge, 1.5-in.-long
ing a misdirected needle thrust. needle and to a 50-mL syringe. The valve on the stopcock
should be open to the needle to allow aspiration of fluid
during needle insertion.
9. Insert the 20-gauge needle (or the catheter-over-needle ap-
PROCEDURES paratus) into the anesthetized tract with the bevel of the
needle down and always aspirate through the syringe as the
General Considerations needle/catheter-over-needle apparatus is slowly advanced.
When pleural fluid is obtained using the needle-only tech-
The most common techniques for performing thoracentesis nique, stabilize the needle by attaching a clamp to the nee-
are catheter-over-needle, needle-only, and needle under direct dle where it exits the skin to prevent further advancement
sonographic guidance. The catheter-through-needle technique of the needle into the pleural space. Once pleural fluid
has been used much less frequently over the past decade. is obtained with the catheter-over-needle technique, direct
the needle-catheter apparatus downward to ensure that the
catheter descends to the most dependent area of the pleu-
ral space. Advance the catheter forward in a single smooth
Technique for Diagnostic motion as the inner needle is simultaneously pulled back
(Needle-Only or Catheter-Over-Needle) out of the chest.
Removal of Freely Flowing Fluid 10. Once pleural fluid can easily be obtained, fill a heparinized
blood gas syringe from the side port of the three-way stop-
The technique for diagnostic removal of freely flowing fluid is cock for measurement of fluid pH [12]. Express all air bub-
as follows: bles from the sample, cap it, and place it in a bag containing
iced slush for immediate transport to the laboratory.
1. Obtain a lateral decubitus chest radiograph to confirm a 11. Fill the 50-mL syringe and transfer its contents into the
free-flowing pleural effusion. appropriate collection tubes and containers [12]. Always
2. Describe the procedure to the patient and obtain written maintain a closed system during the procedure to prevent
informed consent. Operators should be thoroughly famil- room air from entering the pleural space. For most diag-
iar with the procedure they will be performing and should nostic studies, 50 to 100 mL should be ample fluid [1315].
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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98 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

B C D

E F

FIGURE 10.2. Catheter-over-needle technique for thoracentesis of freely flowing pleural field. A: The
patient is comfortably positioned, sitting up and leaning forward over a pillow-draped, height-adjusted,
bedside table. The arms are crossed in front of the patient to elevate and spread the scapulae. The preferred
entry site is along the posterior axillary line. B: The catheter apparatus is gently advanced through the
skin and across the upper surface of the rib. The needle is advanced several millimeters at a time while
continuously aspirating through the syringe. C: As soon as the parietal pleura has been punctured, fluid will
appear in the syringe. D: Before the catheter is advanced any farther, the apparatus is directed downward.
E, F: In rapid sequence, the catheter is advanced fully to the chest wall and the needle withdrawn from
the apparatus. The one-way valve in the apparatus maintains a closed system until the operator manually
changes the position of the stopcock to allow drainage of the pleural fluid.

Always ensure that the three-way stopcock has the valve PTX is suspected by developing signs or symptoms, or mul-
closed toward the patient when changing syringes. tiple needle passes were required [1619].
12. When the thoracentesis is completed, remove the needle (or
catheter) from the patients chest as he or she hums or per-
forms a Valsalva maneuver. Apply pressure to the wound
for several minutes and then apply a sterile bandage. Technique for Therapeutic Removal
13. A routine chest radiograph after thoracentesis is gener- of Freely Flowing Fluid
ally not indicated for most asymptomatic, nonventilated
patients. Obtain a postprocedure upright end-expiratory To perform the technique for therapeutic removal of freely
chest radiograph if air was aspirated during the procedure, flowing fluid, steps 1 to 7 should be followed as described
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 10: Thoracentesis 99

previously. Removal of more than 100 mL pleural fluid gen- should be to classify the effusion as a transudate or an exudate,
erally involves placement of a catheter into the pleural space to using the criteria discussed later. Additional studies can then be
minimize the risk of PTX from a needle during this longer pro- ordered to help establish a final diagnosis for the etiology of
cedure. Commercially available kits generally use a catheter- the pleural effusion, especially in the setting of an exudate.
over-needle system, although catheter-through-needle systems
are still available in some locations. Each kit should have a
specific set of instructions for performing this procedure. Op- Transudates Versus Exudates
erators should be thoroughly familiar with the recommended
procedure for the catheter system that they will be using and A transudate is biochemically defined by meeting all of the fol-
should receive appropriate supervision from an experienced lowing classic (Lights) criteria [24]: pleural fluidserum total
operator before performing thoracentesis on their own. protein ratio of less than 0.5, pleural fluidserum lactate dehy-
drogenase (LDH) ratio of less than 0.6, and pleural fluid LDH
of less than two-thirds the normal serum level. Transudates are
Technique for Thoracentesis generally caused by hydrostatic or oncotic pressure imbalances
by Directed Guidance or from migration of fluid from peritoneal or retroperitoneal
spaces to the pleural space. An exudate is present when any of
Ultrasound guidance has long been used to assist thoracente- the foregoing criteria for transudates is not met. Exudates arise
sis for loculated or small-volume pleural effusions. In recent through a variety of mechanisms that result primarily from in-
years, dynamic (real-time) sonographic scanners have become flammation of the lung or pleura, impaired lymphatic drainage,
more readily available, and coupled with brief physician train- or migration of fluid from the peritoneal space.
ing time, ultrasound-assisted thoracentesis is rapidly becoming A wide variety of alternative diagnostic criteria have been
standard of practice for free-flowing effusions as well [2023]. studied since Lights original work was published. Abbrevi-
The protocol is similar to that described for the needle-only ated criteria with similar diagnostic accuracy, but without the
technique, but the needle can be inserted under direct guid- need for concurrent serum measurements, have been proposed
ance after localization of the effusion. The use of a catheter is [4,25]. Meta-analysis indicates that a classic transudate can
optional in this setting. Of important note is that mandatory be identified with equal accuracy by the combination of both
use of ultrasound for choosing the thoracentesis site and/or for pleural fluid cholesterol of less than 45 mg per dL and a pleural
guiding the procedure, the rate of PTX in one study decreased fluid LDH less than 0.45 times the upper limit of normal for
from 8.6% to 1.1% [21]. serum LDH.
If a transudate is present, generally no further tests on pleu-
Technique for Removal of Freely ral fluid are indicated (Table 10.1). One exception to this is the
transudative pleural effusion due to urinothorax [26]. An aci-
Moving Pneumothorax dotic transudate is characteristic of a urinothorax, and elevated
pleural fluid creatinine confirms the diagnosis. If an exudate is
The technique for removal of freely moving PTX is as follows: identified, further laboratory evaluation is generally warranted
1. Follow the same catheter-over-needle protocol described for (Fig. 10.1). If subsequent testing does not narrow the differen-
removing freely moving fluid, but position the patient supine tial diagnosis and tuberculous pleuritis is a diagnostic consider-
with the head of the bed elevated to 30 to 45 degrees. ation, a percutaneous pleural biopsy should be considered [27].
2. Prepare the second or third intercostal space in the anterior Thoracoscopy-guided pleural biopsy should be considered in
midclavicular line (which avoids hitting the more medial patients with pleural effusion of unknown etiology despite the
internal mammary artery) for the needle and catheter inser- above-listed evaluation.
tion.
3. Have the bevel of the needle facing up and direct the nee-
dle upward so that the catheter can be guided toward the Selected Tests That Are Potentially Helpful to
superior aspect of the hemithorax. Establish Etiology for a Pleural Effusion
4. Air can be actively withdrawn by syringe or pushed out
when intrapleural pressure is supra-atmospheric (e.g., dur-
pH
ing a cough) as long as the catheter is intermittently open to
the atmosphere. In the latter setting, air can leave but not Pleural fluid pH determinations may have diagnostic and ther-
reenter if the catheter is attached to a one-way check-valve apeutic implications [2830]. For instance, the differential di-
apparatus (Heimlich valve) or if it is put to underwater seal. agnosis associated with a pleural fluid pH of less than 7.2 is
5. When local anesthesia and skin cleansing are not possible consistent with systemic acidemia, bacterially infected effusion
because a tension PTX is life threatening, perform the proce- (empyema), malignant effusion, rheumatoid or lupus effusion,
dure without them. If a tension PTX is known or suspected tuberculous effusion, ruptured esophagus, noninfected parap-
to be present and a chest tube is not readily available, quickly neumonic effusion that needs drainage, and urinothorax. Pleu-
insert a 14-gauge needle and 16-gauge catheter according to ral effusions with a pH of less than 7.2 are potentially sclerotic
the above technique to avoid puncturing the lung. If a ten- and require consideration for chest tube drainage to aid reso-
sion PTX is present, air escapes under pressure. When the lution [31,32].
situation has stabilized and the tension PTX has been diag-
nosed, leave the catheter in place until a sterile chest tube Amylase
can be inserted.
A pleural fluid amylase level that is twice the normal serum level
or with an absolute value of greater than 160 Somogyi units
may be seen in patients with acute and chronic pancreatitis,
INTERPRETATION OF PLEURAL pancreatic pseudocyst that has dissected or ruptured into the
FLUID ANALYSIS pleural space, primary and metastatic cancer, and esophageal
rupture. Salivary isoenzymes predominate with malignancy
To determine the etiology of a pleural effusion, a number of and esophageal rupture, whereas intrinsic pancreatic disease
tests on pleural fluid are helpful. The initial determination is characterized by the presence of pancreatic isoenzymes.
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100 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 1 0 . 1
CAUSES OF PLEURAL EFFUSIONS

ETIOLOGIES OF EFFUSIONS THAT ARE VIRTUALLY Malignanciesb


ALWAYS TRANSUDATES Carcinoma
Congestive heart failure Lymphoma
Nephrotic syndrome Mesothelioma
Hypoalbuminemia Leukemia
Urinothorax Chylothorax
Trapped lung Chronically Increased Negative Intrapleural Pressure
Cirrhosis Atelectasis
Atelectasis Trapped lung
Peritoneal dialysis Cholesterol effusion
Constrictive pericarditis
Superior vena caval obstruction Iatrogenic
Drug-induced (nitrofurantoin and methotrexate)
ETIOLOGIES OF EFFUSIONS THAT ARE TYPICALLY EXUDATES Esophageal perforation
Infections Esophageal sclerotherapy
Parapneumonic Central venous catheter misplacement or migration
Tuberculous pleurisy Enteral feeding tube in space
Parasites (amebiasis, paragonimiasis, and echinococcosis) Connective Tissue Disease
Fungal disease Lupus pleuritis
Atypical pneumonias (virus, Mycoplasma, Q fever, and Rheumatoid pleurisy
Legionella) Mixed connective tissue disease
Nocardia and Actinomyces ChurgStrauss syndrome
Subphrenic abscess Wegeners granulomatosis
Hepatic abscess Familial Mediterranean fever
Splenic abscess
Hepatitis Endocrine Disorders
Spontaneous esophageal rupture Hypothyroidismc
Ovarian hyperstimulation syndrome
Noninfectious Inflammations
Pancreatitis Lymphatic Disorders
Benign asbestos pleural effusion Malignancy
Pulmonary embolisma Yellow nail syndrome
Radiation therapy Lymphangioleiomyomatosis
Uremic pleurisy Movement of Fluid from Abdomen to Pleural Space
Sarcoidosis Pancreatitis
Postcardiac injury syndrome Pancreatic pseudocyst
Hemothorax Meigs syndrome
Acute respiratory distress syndrome Carcinoma
Chylous ascites
a
10% to 20% may be transudates.
b
More than 20% are transudates.
c
Occasional transudates.
Adapted from Sahn SA: The pleura. Am Rev Respir Dis 138:184, 1988.

Glucose is normal. Chronic effusions, especially those associated with


rheumatoid and tuberculous pleuritis, are characteristically
A low pleural fluid glucose value is defined as less than
pseudochylous.
50% of the normal serum value. In this situation, the dif-
ferential diagnosis includes rheumatoid and lupus effusion,
bacterial empyema, malignancy, tuberculosis, and esophageal Cell Counts and Differential
rupture [32]. Although pleural fluid white blood cell count and differen-
tial are never diagnostic of any disease, it would be distinctly
Triglyceride and Cholesterol unusual for an effusion other than one associated with bac-
Chylous pleural effusions are biochemically defined by a terial pneumonia to have a white blood cell count exceeding
triglyceride level greater than 110 mg per dL and the pres- 50,000 per L. In an exudative pleural effusion of acute origin,
ence of chylomicrons on a pleural fluid lipoprotein elec- polymorphonuclear leukocytes predominate early, whereas
trophoresis [32]. The usual appearance of a chylous effu- mononuclear cells predominate in chronic exudative effusions.
sion is milky, but an effusion with elevated triglycerides may Although pleural fluid lymphocytosis is nonspecific, severe lym-
also appear serous. The measurement of a triglyceride level is phocytosis (>80% of cells) is suggestive of tuberculosis or ma-
therefore important. Chylous effusions occur when the tho- lignancy. Finally, pleural fluid eosinophilia is nonspecific and
racic duct has been disrupted somewhere along its course. The most commonly associated with either blood or air in the pleu-
most common causes are trauma and malignancy (e.g., lym- ral space.
phoma). A pseudochylous effusion appears grossly milky be- A red blood cell count of 5,000 to 10,000 cells per L
cause of an elevated cholesterol level, but the triglyceride level must be present for fluid to appear pinkish. Grossly bloody
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Chapter 10: Thoracentesis 101

effusions containing more than 100,000 red blood cells per Cytology
mm3 are most consistent with trauma, malignancy, or pul-
Malignancies can produce pleural effusions by implantation
monary infarction. To distinguish a traumatic thoracentesis
of malignant cells on the pleura or impairment of lymphatic
from a preexisting hemothorax, several observations are help-
drainage secondary to tumor obstruction. The tumors that
ful. First, because a preexisting hemothorax has been defibri-
most commonly cause pleural effusions are lung, breast, and
nated, it does not form a clot on standing. Second, a hemotho-
lymphoma. Pleural fluid cytology should be performed for an
rax is suggested when a pleural fluid hematocrit value is 30%
exudative effusion of unknown etiology, using at least 60 to
or more of the serum hematocrit value.
150 mL fluid [13,14,33]. If initial cytology results are neg-
ative and strong clinical suspicion exists, additional samples
Cultures and Stains
of fluid can increase the chance of a positive result to ap-
To maximize the yield from pleural fluid cultures, anaerobic proximately 60% to 70%. The addition of a pleural biopsy
and aerobic cultures should be obtained. Because acid-fast increases the yield to approximately 80%. In addition to malig-
stains may be positive in up to 20% of tuberculous effusions, nancy, cytologic examination can definitively diagnose rheuma-
they should always be performed in addition to Gram-stained toid pleuritis, whose pathognomonic picture consists of slen-
smears. By submitting pleural biopsy pieces to pathology and der, elongated macrophages and giant, round, multinucleated
microbiology laboratories, it is possible to diagnose up to 90% macrophages, accompanied by amorphous granular back-
of tuberculous effusions percutaneously [24]. ground material.

References
1. Seneff MG, Corwin RW, Gold LH, et al: Complications associated with tho- 17. Capizzi SA, Prakash UB: Chest roentgenography after outpatient thoracen-
racentesis. Chest 89:97100, 1986. tesis. Mayo Clin Proc 73:948950, 1998.
2. Collins TR, Sahn SA: Thoracocentesis: clinical value, complications, techni- 18. Doyle JJ, Hnatiuk OW, Torrington KG, et al: Necessity of routine chest
cal problems, and patient experience. Chest 91:817822, 1987. roentgenography after thoracentesis. Ann Intern Med 124:816820, 1996.
3. Grogan DR, Irwin RS, Channick R, et al: Complications associated with tho- 19. Terres RT: Thoracentesis. N Engl J Med 356:641, 2007.
racentesis: a prospective randomized study comparing three different meth- 20. Feller-Kopman D: Therapeutic thoracentesis: the role of ultrasound and pleu-
ods. Arch Intern Med 150:873877, 1990. ral manometry. Curr Opin Pulm Med 13:312318, 2007.
4. Heffner JE, Brown LK, Barbieri CA: Diagnostic value of tests that discrimi- 21. Duncan DR, Morganthaler TI, Ryu JH, et al: Reducing iatrogenic risk in tho-
nate between exudative and transudative pleural effusions. Chest 111:970 racentesis: establishing best practice via experimental training in a zero-risk
980, 1997. environment. Chest 135:13151320, 2009.
5. Romero-Candeira S, Fernandez C, Martin C, et al: Influence of diuretics on 22. Mayo PH, Goltz HR, Tafreshi M, et al: Safety of ultrasound-guided thora-
the concentration of proteins and other components of pleural transudates centesis in patients receiving mechanical ventilation. Chest 125:10591062,
in patients with heart failure. Am J Med 110:681686, 2001. 2004.
6. Bartter T, Mayo PD, Pratter MR, et al: Lower risk and higher yield for thora- 23. Barnes TW, Morgenthaler TI, Olson EJ, et al: Sonographically guided tho-
centesis when performed by experimental operators. Chest 103:18731876, racentesis and rate of pneumothorax. J Clin Ultrasound 33:442446, 2005.
1993. 24. Light RW, MacGregor MI, Luchsinger PC, et al: Pleural effusions: the diag-
7. Colt HG, Brewer N, Barbur E: Evaluation of patient-related and procedure- nostic separation of transudates and exudates. Ann Intern Med 77:507513,
related factors contributing to pneumothorax following thoracentesis. Chest 1972.
116:134138, 1999. 25. Gonlugur U, Gonlugur TE: The distinction between transudates and exu-
8. Raptopoulos V, Davis LM, Lee G, et al: Factors affecting the develop- dates. J Biomed Sci 12:985990, 2005.
ment of pneumothorax associated with thoracentesis. AJR Am J Roentgenol 26. Garcia-Pachon E, Padilla-Navas I: Urinothorax: a case report and review of
156:917920, 1991. the literature with emphasis on biochemical analysis. Respiration 71:533
9. Petersen WG, Zimmerman R: Limited utility of chest radiograph after tho- 536, 2004.
racentesis. Chest 117:10381042, 2000. 27. Maskell NV, Gleeson FJO, Davies R: Standard pleural biopsy versus CT-
10. Wilson MM, Curley FJ: Gas embolism (Pt I). Venous gas emboli. J Intensive guided cutting-needle biopsy for diagnosis of malignant disease in pleural
Care Med 11:182204, 1996. effusions: a randomized controlled trial. Lancet 361:13261330, 2003.
11. Wilson MM, Curley FJ: Gas embolism (Pt II). Arterial gas embolism and 28. Burrows CM, Mathews WC, Colt HG: Predicting survival in patients with re-
decompression sickness. J Intensive Care Med 11:261283, 1996. current symptomatic malignant pleural effusions: an assessment of the prog-
12. Rahman NM, Mishra EK, Davies HE, et al: Clinically important factors in- nostic values of physiologic, morphologic, and quality of life measures of
fluencing the diagnostic measurement of pleural fluid pH and glucose. Am J extent of disease. Chest 117:7378, 2000.
Respir Crit Care Med 178:483490, 2008. 29. Heffner JE, Nietert PJ, Barbieri C: Pleural fluid pH as a predictor of survival
13. Sallach SM, Sallach JA, Vasquez E, et al: Volume of pleural fluid required for patients with malignant pleural effusions. Chest 117:7986, 2000.
for diagnosis of pleural malignancy. Chest 122:19131917, 2002. 30. Heffner JE, Nietert PJ, Barbieri C: Pleural fluid pH as a predictor of pleu-
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of pleural fluid required fro accurate diagnosis of malignant pleural effusion. 31. Heffner JE, Heffner JN, Brown LK: Multilevel and continuous pleural fluid
Chest 135:9991001, 2009. pH likelihood ratios for draining parapneumonic effusions. Respiration
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102 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

CHAPTER 11 ARTERIAL PUNCTURE FOR


BLOOD GAS ANALYSIS
KIMBERLY A. ROBINSON AND RICHARD S. IRWIN

Analysis of a sample of arterial blood for pHa , partial arte- because entry is easiest and pain is minimized. The radial artery
rial carbon dioxide pressure (PaCO2 ), partial arterial oxygen best fulfills the criteria discussed earlier in the chapter; it is very
pressure (PaO2 ), bicarbonate, and percentage oxyhemoglobin superficial at the wrist, and the collateral circulation to the
saturation is performed with an arterial blood gas (ABG) anal- hand by the ulnar artery provides sufficient collateral blood
ysis. Because an ABG can be safely and easily obtained and fur- flow in approximately 92% of normal adults in the event of
nishes rapid and accurate information on how well the lungs total occlusion of the radial artery [6].
and kidneys are working, it is the single most useful labora- The absence of a report of total occlusion of the radial artery
tory test in managing patients with respiratory and metabolic after puncture for ABG in an adult with normal hemostasis and
disorders. One should not rely on oximetry alone to evalu- the absence of significant peripheral vascular disease attest to
ate arterial oxygen saturation (SaO2 ) fully. Given the shape the safety of the percutaneous arterial puncture. It also suggests
of the oxyhemoglobin saturation curve, there must be a sub- that determining the adequacy of collateral flow to the superfi-
stantial fall in PaO2 before SaO2 is altered to any apprecia- cial palmar arch by Allens test [7], a modification of Allens test
ble degree, and it is not possible to predict the level of PaO2 [8] (see Chapter 3), or Doppler ultrasound [6] before puncture
and PaCO2 reliably using physical signs such as cyanosis [1] is not routinely necessary in patients with normal hemostasis
and depth of breathing [2]. In addition, a discrepancy between and the absence of significant peripheral vascular disease. If
SaO2 measured by pulse oximetry and that calculated by the radial artery sites are not accessible, dorsalis pedis, posterior
ABG can aid in the diagnosis of carboxyhemoglobinemia and tibial, superficial temporal (in infants), brachial, and femoral
methemoglobinemia. arteries are alternatives (see Chapter 3).
Unsuspected hypoxemia or hypercapnia (acidemia) can
cause a constellation of central nervous system and cardiovas-
cular signs and symptoms. The clinician should have a high
index of suspicion that a respiratory or metabolic disorder, or Contraindications
both, is present in patients with these findings and is most ap-
propriately evaluated by obtaining an ABG. Although acute hy- Brachial and especially femoral artery punctures are not ad-
percapnia to 70 mm Hg (pH 7.16) and hypoxemia to less than vised in patients with abnormal hemostatic mechanisms be-
30 mm Hg may lead to coma and circulatory collapse, chronic cause adequate vessel tamponade may not be possible in that
exposures permit adaptation with more subtle effects [3]. Thus, these vessels are not located superficially, risking greater chance
the ABG provides the most important way of making a diagnos- of complications [9]. If frequent sampling of superficial arteries
tic assessment regarding the nature and severity of a respiratory in the same situation becomes necessary, arterial cannulation
or metabolic disturbance and of following its course over time. is recommended (see Chapter 3). Moreover, any vessel that has
Normal range of values for pHa is 7.35 to 7.45 and for been reconstructed surgically should not be punctured for fear
PaCO2 , 35 to 45 mm Hg [4]. For PaO2 , the accepted predictive of forming a pseudoaneurysm, compromising the integrity of
regression equation in nonsmoking, upright, normal individu- an artificial graft site or seeding the foreign body that could be-
als aged 40 to 74 years is as follows [5]: PaO2 = 108.75 come a nidus for infection. This should also include avoidance
(0.39 age in years). of a femoral arterial puncture on the same side as a transplanted
kidney.
The conventional recommended radial artery technique is
as follows:
DRAWING THE ARTERIAL BLOOD
1. Put on protective gloves and sit in a comfortable position
GAS SPECIMEN facing the patient.
2. With the patients hand supinated and the wrist slightly
Percutaneous Arterial Puncture hyperextended, palpate the radial artery. Severe hyperex-
tension may obliterate the pulse.
The conventional technique of sampling arterial blood using a 3. Cleanse the skin with an alcohol swab.
glass syringe is described in detail, because it is the standard to 4. With a 25-gauge needle, inject enough 1% lidocaine intra-
which all other methods are compared. The pulsatile arterial dermally to raise a small wheal at the point where the skin
vessel is easily palpated in most cases. If a large enough needle puncture is to be made. The local anesthetic makes subse-
is used, entry is apparent as the syringe fills spontaneously by quent needle puncture with a 22-gauge needle less painful
the pressurized arterial flow of blood, without the need for and often painless [10]. If local anesthesia is not given,
applying a vacuum or using a vacuum-sealed collecting tube. however, the potential pain and anxiety, if associated with
It is logical to preferentially enter arteries that have the best breath holding, may cause substantial blood gas changes.
collateral circulation so that if spasm or clotting occurs, the Thirty-five seconds of breath holding in normal subjects
distal tissue is not deprived of perfusion. Logic also dictates that has been associated with a fall in PaO2 of 50 mm Hg and
puncture of a site where the artery is superficial is preferable, a pH of 0.07 and a rise in PaCO2 of 10 mm Hg [11].
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Chapter 11: Arterial Puncture for Blood Gas Analysis 103

5. Attach a needle no smaller than 22 gauge to a glass syringe 5. Unintentional sampling of a vein normally causes a falsely
that can accept 5 mL blood. low PaO2 . A venous PO2 greater than 50 mm Hg can be ob-
6. Wet the needle and syringe with a sodium heparin solution tained if the sampling area is warmed. The PO2 of arterial-
(1,000 units per mL). Express all excess solution. ized venous blood can approximate PaO2 when blood flow
7. With the needle, enter the artery at an angle of approxi- is greatly increased by warming, compromising the time for
mately 30 degrees to the long axis of the vessel. This in- peripheral oxygen extraction.
sertion angle minimizes the pain associated with uninten-
tional contact with the periosteum below the artery.
8. As soon as the artery is entered, blood appears in the sy- Complications
ringe. Allow the arterial pressure to fill the syringe with at
least 3 mL of blood. Do not apply suction by pulling on Using the conventional radial artery technique described ear-
the syringe plunger. lier in the chapter, complications are unusual. They include a
9. Immediately after obtaining the specimen, expel any tiny rare vasovagal episode, local pain, and limited hematomas. An
air bubbles to ensure that the specimen will be anaerobic expanding aneurysm of the radial artery and reflex sympathetic
and then cap the syringe. dystrophy [22] have been reported even more rarely after fre-
10. Roll the blood sample between both palms for 5 to 15 quent punctures [23].
seconds to mix the heparin and blood. Apply pressure to
the puncture site for 5 minutes or longer, depending on
the presence of a coagulopathy. If the arterial sample was
obtained from the brachial artery, compress this vessel so MEASUREMENTS FROM THE
that the radial pulse cannot be palpated. ARTERIAL BLOOD GAS SPECIMEN
11. Immerse the capped sample in a bag of ice and water (slush)
and immediately transport it to the blood gas laboratory. Although pH, PCO2 , PO2 , bicarbonate, and SaO2 are all usu-
12. Write on the ABG slip the time of drawing and the condi- ally reported, it is important to understand that the bicarbonate
tions under which it was drawn (e.g., fraction of inspired and SaO2 are calculated, not directly measured. Although the
oxygen, ventilator settings, and the patients position and calculated bicarbonate value is as reliable as the measured pH
temperature). and PCO2 values, given their immutable relationship through
the HendersonHasselbalch equation, the calculated SaO2 is
Deviations from these recommended techniques may intro-
often inaccurate because of the many variables that cannot be
duce the following errors:
corrected (e.g., 2,3-diphosphoglycerate and binding character-
1. The syringe material may influence the results of PaO2 [12 istics of hemoglobin).
14]. The most accurate results have been consistently ob- The patient in the intensive care unit often requires serial
tained using a glass syringe. If plastic is used, the following ABG measurements to follow the progression of critical illness
errors may occur: (a) falsely low PaO2 values may be ob- and guide therapy. Although it is understandable to interpret
tained because plastic allows oxygen to diffuse to the atmo- fluctuations in the ABG data as a sign of the patients condi-
sphere from the sample whenever the PO2 exceeds 221 mm tion worsening or improving, depending on the trend, it is also
Hg; (b) plastic syringes with high surface area to volume ra- important to appreciate that modest fluctuations may be due
tios (e.g., 1-mL tuberculin syringes) worsen gas permeabil- to deviations in the collection of the ABG specimen. Therefore,
ity errors as compared to standard 3-mL syringes. For this routine monitoring of ABGs without an associated change in
reason, butterfly infusion kits with their long, thin tubing patient status may not be warranted and may lead to an un-
should not be used [15]; (c) plastic syringes tenaciously re- productive, lengthy, and expensive search for the cause.
tain air bubbles, and extra effort is necessary to remove them When electrolytes and other blood values are measured
[13]; (d) plastic impedes smooth movement of the plunger from the unused portion of an ABG sample, clinicians should
that can have an impact on the clinicians confidence that be aware of the following: Traditional liquid and crystalline
arterial rather than venous blood has been sampled. heparins for ABG sampling are sodium-heparin salts that ar-
2. If suction is applied for plunger assistance, gas bubbles may tificially increase plasma sodium concentrations. Calcium and
be pulled out of the solution. If they are expelled, measured potassium bind to the negatively charged heparins, spuriously
PaO2 and PaCO2 tensions may be falsely lowered [16]. lowering their values. Lithium or electrolyte-balanced heparin
3. Although liquid heparin is a weak acid, plasma pH is not is now available that contains physiologic concentrations of
altered because it is well buffered by hemoglobin. Mixing sodium and potassium that should be used whenever sodium,
liquid heparin with blood dilutes dissolved gasses, shifting potassium, ionized magnesium, ionized calcium, chloride, glu-
their concentration to that of heparin (PO2 approximately cose, and lactate are measured in an ABG specimen [2426].
150 mm Hg and PCO2 less than 0.3 mm Hg at sea level and Although lithium or electrolyte-balanced heparin minimizes the
room temperature). The degree of alteration depends on the errors in electrolyte concentrations, dilutional error may still
amount of heparin relative to blood and the hemoglobin exist if excessive amounts are used for anticoagulation.
concentration [1619]. The dilutional error is no greater By convention, ABG specimens are analyzed at 37 C. Al-
than 4% if a glass syringe and 22-gauge needle are only though no studies have demonstrated that correction for the pa-
wetted with approximately 0.2 mL heparin and 3 to 5 mL tients temperature is clinically necessary, blood gases drawn at
blood collected. Any less heparin risks a clotted and unus- temperatures greater than 39 C should probably be corrected
able sample. Dilutional errors are avoided with the use of for temperature [27]. Because the solubility of oxygen and car-
crystalline heparin, but this preparation is difficult to mix bon dioxide increases as blood is cooled to 37 C, the hyper-
and increases the risk of clotting the specimen. thermic patient is more acidotic and less hypoxemic than uncor-
4. If an ABG specimen is not analyzed within 1 minute of be- rected values indicate. Therefore, for each 1 C that the patients
ing drawn or not immediately cooled to 2 C, the PO2 and temperature is greater than 37 C, PaO2 should be increased
pH fall and PCO2 rises because of cellular respiration and 7.2%, PaCO2 increased 4.4%, and pH decreased 0.015. Tem-
consumption of oxygen by leukocytes, platelets, and retic- perature correction for pH and PaCO2 in the hypothermic pa-
ulocytes [20]. This is of particular concern in patients with tient is controversial. Although correction back to the patients
leukemia (leukocytes greater than 40 109 per L) or throm- temperature may result in better preservation of cerebral blood
bocytosis (1,000 109 per L) [21]. flow, intracranial pressure can be adversely affected in selected
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104 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

populations. The reader is referred elsewhere for more infor- TA B L E 1 1 . 1


mation [28]. However, PaO2 values must be corrected for tem-
perature lest significant hypoxemia be overlooked. The PaO2 RELATION BETWEEN [H+ ] AND PH OVER A NORMAL
at 37 C is decreased by 7.2% for each degree that the patients RANGE OF PH VALUESa
temperature is less than 37 C.
It should also be noted that transport of an ABG specimen pH [H+ ] (nM/L)
to the laboratory via a pneumatic tube system can result in al-
terations in PaO2 secondary to contamination with room air. 7.36 44
This effect is presumed to be due to pressure changes within the 7.37 43
pneumatic tube system because the use of pressure-tight trans- 7.38 42
port containers obliterates the effect [29]. If a pneumatic tube 7.39 41
system is to be used, one must be sure that all air bubbles are 7.40 40
carefully expelled from the ABG specimen and that a pressure-
tight transport container is used. Otherwise, it may be best to 7.41 39
hand-carry samples to the laboratory [2931]. 7.42 38
7.43 37
7.44 36

PHYSICIAN RESPONSIBILITY a
Note that pH 7.40 corresponds to hydrogen ion concentration of
40 nM/L and that, over the small range shown, each deviation in pH
Even when the ABG values of pH, PCO2 , PO2 , and bicarbon- of 0.01 units corresponds to opposite deviation in [H+ ] of 1 nM/L.
ate appear consistently reliable, the clinician should periodi- For pH values between 7.28 and 7.45, [H+ ] calculated empirically in
this fashion agrees with the actual value obtained by means of
cally check the accuracy of the blood gas samples because the logarithms to the nearest nM/L (nearest 0.01 pH unit). However, in
bicarbonate is calculated, not directly measured. Aliquots of ar- the extremes of pH values, less than pH 7.28 and greater than pH
terial blood can be sent simultaneously for ABG analysis and 7.45, the estimated [H+ ] is always lower than the actual value, with
to the chemistry laboratory for a total (T) CO2 content. Accu- the discrepancy reaching 11% at pH 7.10 and 5% at pH 7.50.
racy of the blood gas laboratorys values can be checked using Modified from Kassirer J, Bleich H: Rapid estimation of plasma
Hendersons simple mathematical equation that is a rearrange- carbon dioxide tension from pH and total carbon dioxide content.
N Engl J Med 171:1067, 1965.
ment of the HendersonHasselbalch equation: [H+ ] = 25
PaCO2 /HCO +
3 . [H ] is solved by using the pH measured in the
blood gas laboratory (Table 11.1). Measured arterial TCO2
should be close to the calculated bicarbonate value. Venous and acidbase status have been identified, pulse oximetry can
TCO2 should not be used in this exercise because it is often be used to follow trends in SaO2 in stable or improving patients
and normally up to 5 mEq per L greater than arterial TCO2 . because serial ABGs are costly and risk vessel injury with re-
peated arterial punctures.
Some progress has been made in the area of noninvasive
ALTERNATIVES measurement of gas exchange. This includes oximetry, tran-
scutaneous PO2 and PCO2 (Ptc CO2 ) measurement, end-tidal
Many situations may arise whereby arterial blood samples are CO2 , and indwelling intravascular electrode systems. Measure-
not available. For example, severe peripheral vascular disease ment of end-tidal CO2 requires a closed system of gas collec-
makes radial arterial puncture difficult, or the patient refuses tion (i.e., ventilator circuit or noninvasive mask ventilation)
arterial blood sampling or cannulation. In general, in the ab- that is not always possible. Thus, there has been increased fo-
sence of circulatory failure or limb ischemia, central and pe- cus on transcutaneous measurement of carbon dioxide tension.
ripheral venous blood may substitute for arterial when mon- These systems require localized heating of the skin by a heat-
itoring acidbase and ventilatory status. In hemodynamically ing element to increase local perfusion. Studies have suggested
stable patients, pHa is, on average, 0.03 units higher than cen- improvement in the ability of transcutaneous systems to accu-
tral venous pH (pHcv ) and PaCO2 is lower than central ve- rately assess SpO2 and Ptc CO2 in critically ill patients as long
nous carbon dioxide (Pcv CO2 ) by 5 mm Hg [32], and changes as the PaCO2 is less than 56 mm Hg [34,35].
in each are tightly correlated [33]. Regression analysis re-
veals pHa = (1.027 pHcv ) 0.156 and PaCO2 = (0.754
Pcv CO2 ) + 2.75. In shock, the accentuated discrepancy may POINT-OF-CARE TESTING
be due to increased carbon dioxide generated by the buffer-
ing of acids in conditions characterized by increased lactic acid Blood gas analysis is now routinely performed at the bed-
production. side with point-of-care testing (POCT) devices. Advantages of
It must be made clear that in the absence of warming a POCT include convenience and rapid turnaround time, the-
sampling area to collect arterialized venous blood, an arte- oretically improving the quality of patient care. With regard
rial sample is still necessary for evaluation of accurate oxy- to pH, PO2 , and PCO2 , several studies have verified a high
genation status for precise measurements of PO2 and alveolar correlation between POCT results and conventional analysis
arterial oxygen gradient determination. Once the oxygenation methods [36,37].

References
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olar ventilation. Am Rev Respir Dis 98:868, 1968. sion in the middle-aged and elderly. Am J Respir Crit Care Med 152:934,
3. Weiss E, Faling L, Mintz S, et al: Acute respiratory failure in chronic ob- 1995.
structive pulmonary disease I. Pathophysiology. Disease-a-Month 1, October 6. Felix WJ, Sigel B, Popky G: Doppler ultrasound in the diagnosis of peripheral
1969. vascular disease. Semin Roentgenol 4:315, 1975.
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Chapter 12: Tracheostomy 105

7. Allen E: Thromboangiitis obliterans: methods of diagnosis of chronic occlu- 23. Mathieu A, Dalton B, Fischer J, et al: Expanding aneurysm of the radial
sive arterial lesions distal to the wrist, with illustrative cases. Am J Med Sci artery after frequent puncture. Anesthesiology 38:401, 1973.
178:237, 1929. 24. Burnett R, Covington A, Fogh-Anderson N: Approved IFCC recommen-
8. Bedford R: Radial arterial function following percutaneous cannulation with dations on whole blood sampling, transport and storage for simultaneous
18- and 20-gauge catheters. Anesthesiology 47:37, 1977. determination of pH, blood gases and electrolytes. Eur J Clin Chem Clin
9. Macon WI, Futrell J: Median-nerve neuropathy after percutaneous puncture Biochem 33:247, 1995.
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288:1396, 1973. with the simultaneous measurement of ionized magnesium and ionized cal-
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19. Bloom S, Canzanello V, Strom J, et al: Spurious assessment of acid-base status 34. Senn O, Clarenbach CF, Kaplan V, et al: Monitoring carbon dioxide tension
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21. Schmidt C, Mullert-Plathe O: Stability of Po2 , Pco2 and pH in heparinized bon dioxide measurements for assessing long-term mechanical ventilation.
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1995. laboratories. Eur Respir J 10(6):1341, 1997.

CHAPTER 12 TRACHEOSTOMY
SCOTT E. KOPEC AND TIMOTHY A. EMHOFF

Although reports of performing tracheostomy date back to the (ICU). The prevalence of tracheostomies in ICU patients ranges
first century bc [1], it was not performed regularly until the from 8% to more than 30% [2,3].
1800s when used by Trousseau and Bretonneau in the man- In this chapter we review the indications, contraindications,
agement of diphtheria. In the early 1900s, this procedure was complications, and techniques associated with tracheostomy.
used to treat difficult cases of respiratory paralysis from po- We also discuss the timing of converting an orally intubated
liomyelitis. Largely because of improvements in tubes and ad- patient to tracheostomy.
vances in clinical care, endotracheal intubation has become the
treatment of choice for short-term airway management.
Although tracheostomy is occasionally required in critically INDICATIONS
ill and injured patients who cannot be intubated for various
reasons (e.g., cervical spine injury, upper airway obstruction, The indications for tracheostomy can be divided into three gen-
laryngeal injury, and anatomic considerations), the most com- eral categories: (i) to bypass obstruction of the upper airway, (ii)
mon use of this procedure today is to provide long-term access to provide an avenue for tracheal toilet and removal of retained
to the airway in patients who are dependent on mechanical ven- secretions, and (iii) to provide a means for ventilatory support.
tilation. With improvements in critical care medicine over the These indications are summarized in Table 12.1 [410].
past 30 years, more patients are surviving the initial episodes of Anticipated prolonged ventilatory support, especially pa-
acute respiratory failure, trauma, and extensive surgeries and tients receiving mechanical ventilation via translaryngeal in-
are requiring prolonged periods of mechanical ventilation. It is tubation, is the most common indication for placing a tra-
now common practice to expeditiously convert these patients cheostomy in the ICU. There are several advantages and
from translaryngeal intubation to tracheostomy. Tracheostomy disadvantages of both translaryngeal intubation and tra-
is becoming a very common procedure in the intensive care unit cheostomy in patients requiring prolonged ventilator support,
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106 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 1 2 . 1
INDICATIONS FOR TRACHEOSTOMY [410]

Upper airway obstruction


Laryngeal dysfunction: Vocal cord paralysis
Trauma: Upper airway obstruction due to hemorrhage, edema, or crush injury; unstable mandibular fractures; injury to the larynx;
cervical spine injuries
Burns and corrosives: Hot smoke, caustic gases, corrosives
Foreign bodies
Congenital anomalies: Stenosis of the glottic or subglottic area
Infections: Croup, epiglottitis, Ludwigs angina, deep neck space infections
Neoplasms: Laryngeal cancer
Postoperative: Surgeries of the base of the tongue and hypopharynx; rigid fixation of the mandibular
Obstructive sleep apnea
Tracheal toilet
Inability to clear secretions: Generalized weakness, altered mental status, excess secretions
Neuromuscular disease
Ventilatory support: Prolonged or chronic

Kremer B, Botos-Kremer A, Eckel H, et al: Indications, complications, and surgical technique for pediatric tracheostomies. J Pediatr Surg 37:1556, 2002.
Bjure J: Tracheotomy: A satisfactory method in the treatment of acute epiglottis. A clinical and functional follow-up study. Int J Pediatr
Otorhinolaryngol 3:37, 1981.
Hanline MH Jr: Tracheotomy in upper airway obstruction. South Med J 74:899, 1981.
Taicher S, Givol M, Peleg M, et al: Changing indications for tracheostomy in maxillofacial trauma. J Oral Maxillofac Surg 54:292, 1996.
Guilleminault C, Simmons FB, Motta J, et al: Obstructive sleep apnea syndrome and tracheostomy. Arch Intern Med 141:985, 1981.
Burwell C, Robin E, Whaley R, et al: Extreme obesity associated with alveolar hypoventilation. Am J Med 141:985, 1981.
Yung MW, Snowdon SL: Respiratory resistance of tracheostomy tubes. Arch Otolaryngol 110:591, 1984.

and these are summarized in Table 12.2 [1113]. Most authors more than 1 week with regard to receiving a tracheostomy or
feel that when the procedure is performed by a skilled surgical continuing with an endotracheal tube [2,3].
group, the potential benefits of tracheostomy over translaryn-
geal intubation for most patients justify the application despite
its potential risks. However, there are no detailed clinical tri- CONTRAINDICATIONS
als consistently confirming the advantages of tracheostomy in
patients requiring prolonged mechanical ventilation. In a ret- There are no absolute contraindications to tracheostomy. Rel-
rospective and a nonrandomized study, there were conflicting ative complications include uncorrected coagulopathy, high
data regarding mortality in patients with respiratory failure of levels of ventilator support (i.e., high levels of positive

TA B L E 1 2 . 2
ADVANTAGES AND DISADVANTAGES OF INTUBATION AND TRACHEOSTOMY
[1113]

Translaryngeal intubation
Advantages Disadvantages
Reliable airway during urgent intubation Bacterial airway colonization
Avoidance of surgical complications Inadvertent extubation
Lower initial cost Laryngeal injury
Tracheal stenosis
Purulent sinusitis (nasotracheal intubations)
Patient discomfort
Tracheostomies
Advantages Disadvantages
Avoids direct injury to the larynx Complications (see Table 12.3)
Facilitates nursing care Bacterial airway colonization
Enhances patient mobility Cost
More secure airway Surgical scar
Improved patient comfort Tracheal and stomal stenosis
Permits speech
Provides psychologic benefit
More rapid weaning from mechanical
ventilation
Better oral hygiene
Decreased risk of nosocomial pneumonia
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Chapter 12: Tracheostomy 107

end-expiratory pressure [PEEP]), and abnormal anatomy of associated with placing a tracheostomy, plus the advantages
the upper airway. However, a prospective cohort study has and disadvantages of both translaryngeal intubation and tra-
demonstrated that percutaneous tracheostomy can be safely cheostomy. In summary, if a patient remains ventilator depen-
preformed in patients with refractory coagulopathy from liver dent after a week of translaryngeal intubation, a tracheostomy
disease [14]. Morbidly obese patients with body mass index can be considered. Whether to perform the procedure or not
greater than 30 kg per m2 also appear to be at higher risk for should depend on the anticipated duration of ventilatory sup-
complications with both open tracheostomy [15] and percuta- port and the benefits of a tracheostomy in that specific patient.
neous tracheostomy [16]. In patients with severe brain injury, If the patient appears to have minimal barriers to weaning and
percutaneous tracheostomy can be safely performed without appears likely to be successfully weaned and extubated within
significantly further increasing intracranial pressure [17]. 7 days, tracheostomy should be avoided. In those patients
Certain conditions warrant special attention before anes- whom it appears unlikely that they will successfully be weaned
thesia and surgery. In patients undergoing conversion from and extubated in 7 days, tracheostomy should be strongly con-
translaryngeal intubation to a tracheostomy for prolonged ven- sidered. For those patients whose ability to wean and be ex-
tilatory support, the procedure should be viewed as an elective tubated is unclear, the patients status should be readdressed
or semielective procedure. Therefore, the patient should be as daily [11].
medically stable as possible, and all attempts should be made Over the past several years there has been momentum to per-
to correct the existing coagulopathies, including uremia. Venti- form a tracheostomy early, that is, after 1 week of mechanical
lator settings should be reduced to where tube exchange during ventilation. Fueling this was a meta-analysis [20], which sug-
the tracheostomy is safe because during the exchange positive gested advantages to early tracheostomy, performed within
pressure is temporarily lost for some period of time. If not al- 7 days of translaryngeal intubation over a late tracheostomy
ready on 5 cm H2 O of PEEP, placing the patient supine and (>7 days) in critically ill patients requiring mechanical ventila-
using 5 or 7.5 cm H2 O of PEEP temporarily is a good test tion. The meta-analysis combined five prospective studies and
to decide if the patient will tolerate the exchange. For obvious included 406 patients and suggested that early tracheostomy
reasons, emergent tracheostomies for upper airway obstruction resulted in a decrease in length of ICU stay by an average of
may need to be preformed when the patient is unstable or has 15.3 days and a decrease in duration of mechanical ventila-
a coagulopathy. tion by an average of 8.5 days [20]. Potential reasons for the
decrease in duration of mechanical ventilation include easier
weaning due to less dead space, less resistance, and less obstruc-
TIMING OF TRACHEOSTOMY tion due to mucus plugging in patients with tracheostomies.
There was no significant increase in hospital mortality or risk of
When to perform a tracheostomy on an intubated, critically hospital-acquired pneumonia. However, there are obvious lim-
ill patient has continued to remain very controversial. Older itations to the meta-analysis. Since this meta-analysis, several
recommendations range from performing a tracheostomy af- other studies have revealed conflicting data. Table 12.3 summa-
ter just 3 days of translaryngeal intubation due to the risk of rizes several studies comparing early versus late tracheostomy
mucosal damage to the larynx and vocal cords [18] to more [2028]. In summary, it remains unclear if early tracheostomy
than 21 days on the basis of reported high complication rates has any impact on mortality, length of ICU stay, days on
of open tracheostomies [19]. In 2003, Heffner recommended a mechanical ventilation, or ventilatory-associated pneumonia.
more up-to-date approach regarding the timing of converting Until more definitive data are available, Heffners 2003 recom-
an intubated patient to a tracheostomy [11]. This recommenda- mendations [11] appear to make the most sense for most med-
tion takes into account the very low mortality and morbidity ical and surgical patients on prolonged mechanical ventilation.

TA B L E 1 2 . 3
STUDIES EVALUATING EARLY (7 DAYS) VERSUS LATE (>7 DAYS) TRACHEOSTOMY

No. of
Study patients Study type Patient type Results

Rodriquez et al., 1990 106 Prospective Surg Decreased ICU LOS and MV days with early tracheostomy
Randomized
Sugarman et al., 1997 127 Prospective Surg, Trauma No difference in mortality, VAP rate, or ICU LOS
Randomized
Brook et al., 2000 90 Prospective Med, Surg Decreased MV days and hospital costs
Observational
Rumbak et al., 2004 120 Prospective Med Decreased mortality, VAP 2004 rate, ICU LOS, and MV
days with early trach
Griffiths et al., 2005 Meta-analysis Med, Surg Decreased MV days and ICU LOS with early trach, no
difference in mortality or VAP rate
Scales et al., 2008 10,927 Retrospective Med, Surg Decreased mortality, MV days, ICU LOS with early trach
Cohort
Blot et al., 2008 123 Prospective Med, Surg No difference in mortality, VAP rate, or ICU LOS
Randomized
Durbin et al., 2010 641 Meta-analysis Med, Surg No difference in mortality, VAP rate, or MV days
Terragni et al., 2010 419 Prospective Med, Surg No difference in VAP rate ICU LOS or mortality, but
Randomized decreased MV days

LOS, length of stay; Med, medicine patients; MV, mechanical ventilation; Surg, surgery patients; VAP, ventilator-associated pneumonia.
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108 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

Early tracheostomy may be beneficial in some specific in- airway in an emergency when oral or nasotracheal intubation is
stances. Patients with blunt, multiple-organ trauma have a nonsuccessful or contraindicated. The cricothyroid membrane
shorter duration of mechanical ventilation, fewer episodes of is higher in the neck than the tracheal rings and therefore closer
nosocomial pneumonia [29], and a significant reduction in hos- to the surface and more accessible. In emergency situations,
pital costs [30] when the tracheostomy is performed within translaryngeal intubations fail because of massive oral or nasal
1 week of their injuries. Similar benefits have been reported in hemorrhage or regurgitation, structural deformities of the up-
patients with head trauma and poor Glasgow Coma Score [31 per airway, muscle spasm and clenched teeth, and obstruction
33], acute spine trauma [34,35], and thermal injury [36] if a by foreign body through the upper airway [52]. Cricothyro-
tracheostomy is performed within a week after the injury. Also, tomy finds its greatest use in trauma management, axial or
patients with facial injuries may require early tracheostomy to suspected cervical spine injury, alone or in combination with
allow or facilitate facial fracture surgery, fixation, and immo- severe facial trauma, where nasotracheal and orotracheal in-
bilization. tubation is both difficult and hazardous. Thus cricothyrotomy
has an important role in emergency airway management [53].

PROCEDURES Use and Contraindications


Cricothyrotomy should not be used to manage airway ob-
Emergency Tracheostomy struction that occurred immediately after endotracheal extu-
bation because the obstruction may be found below the larynx
Emergency tracheostomy is a moderately difficult procedure [41,43,53]; likewise, with primary laryngeal trauma or diseases
requiring training and skill, experience, adequate assistance, such as tumor or an infection, cricothyrotomy may prove to be
time, lighting, and proper equipment and instrumentation. useless. It is contraindicated in infants and children younger
When time is short, the patient is uncooperative, anatomy is than 10 to 12 years under all circumstances because steno-
distorted, and the aforementioned requirements are not met, sis and even transection are possible [53]. In this age group,
tracheostomy can be very hazardous. Emergency tracheostomy percutaneous transtracheal ventilation may be a temporizing
comprises significant risks to nearby neurovascular structures, procedure until the tracheostomy can be performed.
particularly in small children in whom the trachea is small and
not well defined. The risk of complications from emergency Anatomy
tracheostomy is two to five times higher than for elective tra-
The cricothyroid space is no larger than 7 to 9 mm in its
cheostomy [37,38]. Nonetheless, there are occasional indica-
vertical dimension, smaller than the outside diameter of most
tions for emergency tracheostomy [39], including transected
tracheostomy tubes (outside diameter 10 mm). The cricothy-
trachea, anterior neck trauma with crushed larynx [40], severe
roid artery runs across the midline in the upper portion, and
facial trauma, acute laryngeal obstruction or near-impending
the membrane is vertically in the midline. The anterior supe-
obstruction, and pediatric (younger than 12 years) patients re-
rior edge of the thyroid cartilage is the laryngeal prominence.
quiring an emergency surgical airway in whom an cricothyro-
The cricothyroid membrane is approximately 2 to 3 cm be-
tomy is generally not advised. In emergency situations when
low the laryngeal prominence and can be identified as an in-
there is inadequate time or personnel to perform an emergency
dentation immediately below the thyroid cartilage. The lower
tracheostomy, a cricothyrotomy may be a more efficient and
border of the cricothyroid membrane is the cricoid cartilage
expedient manner to provide an airway.
[47,48,52,55]. A description of the cricothyrotomy procedure
is contained in standard surgical texts.
Cricothyrotomy Complications
Cricothyrotomy (cricothyroidotomy) was condemned in Jack- The report of incidents of short- and long-term complica-
sons [41] 1921 article on high tracheostomies because of ex- tions of cricothyrotomy ranges from 6.1% [43] for proce-
cessive complications, particularly subglottic stenoses [42]. He dures performed in elective, well-controlled, carefully selected
emphasized the importance of the cricoid cartilage as an encir- cases to greater than 50% [53,56] for procedures performed
cling support for the larynx and trachea. However, a favorable under emergency or other suboptimal conditions. The inci-
report of 655 cricothyrotomies, with complication rates of only dence of subglottic stenosis after cricothyrotomy is 2% to 3%
6.1% and no cases of subglottic stenoses [43], prompted reeval- [42,44]. This major complication occurs at the tracheostomy
uation of cricothyrotomy for elective and emergency airway or cricothyrotomy site, but not at the cuff site [57]. Necrosis
access. Further reports emphasized the advantages of cricothy- of cartilage due to iatrogenic injury to the cricoid cartilage or
rotomy over tracheostomy. These include technical simplicity, pressure from the tube on the cartilage may play a role [54].
speed of performance, low complication rate [4347], suit- Possible reasons that subglottic stenoses may occur more com-
ability as a bedside procedure, usefulness for isolation of the monly with cricothyrotomy than with tracheostomy are as fol-
airway for median sternotomy [46,48], radical neck dissec- lows: the larynx is the narrowest part of the laryngotracheal
tion [49], lack of need to hyperextend the neck, and forma- airway; subglottic tissues, especially in children, are intoler-
tion of a smaller scar. Also, because cricothyrotomy results ant of contact; and division of the cricothyroid membrane and
in less encroachment on the mediastinum, there is less chance cricoid cartilage destroy the only complete rings supporting the
of esophageal injury and virtually no chance of pneumotho- airway [42]. Furthermore, the range of tube sizes is limited due
rax or tracheal arterial fistula [47]. Despite these considera- to the rigidity of the surrounding structures (cricoid and thy-
tions, many authorities currently recommend that cricothy- roid cartilage), and the curvature of the tracheostomy tube at
rotomy should be used as an elective long-term method of this level may obstruct the airway due to potential posterior
airway access only in highly selective patients [41,43,4951]. membrane impingement [58]. Prior laryngotracheal injury, as
Use of cricothyrotomy in the emergency setting, particularly with prolonged translaryngeal intubation, is a major risk factor
for managing trauma, is not controversial [5254]. Emergency for the development of subglottic stenosis after cricothyrotomy
cricothyrotomy is useful because it requires a small number of [42,44].
instruments and less training than tracheostomy and can be The association of cricothyrotomy with these possible
performed quickly as indicated as a means of controlling the complications leads most authorities to consider replacing a
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Chapter 12: Tracheostomy 109

cricothyrotomy within 48 to 72 hours with a standardized tra- lished between 1991 and 1999 totaling 236 patients and con-
cheostomy procedure. This is commonly done by an open sur- cluded that there is no difference in mortality between PDT and
gical tracheostomy (OST), which occurs between the second OST, and PDT was associated with less bleeding and stomal
and third tracheal rings, as compared to a percutaneous dila- infections and was performed quicker. Delancy et al. [67] also
tional tracheostomy (PDT), which usually occurs between the concluded that there was no significant difference in mortality
cricoid cartilage and the first ring or the first and second rings and major complications between PDT and OST in a meta-
[58]. analysis consisting of 17 randomized trials and a total of 1,212
patients. They also showed a decrease in stomal infections in
the PDT group, but no difference in bleeding complications.
TRACHEOSTOMY PROCEDURES Similar findings were demonstrated by meta-analysis studies
by Higgins and Punthakee [68] and Oliver et al. [69]. How-
IN THE INTENSIVE CARE UNIT ever, Dulguerov et al. [70] reviewed 3,512 patients from 48
studies performed between 1960 and 1996 and concluded that
Tracheostomy is one of the most common surgical ICU proce- OST was more favorable than PDT. Subsequent critiques of
dures and is commonly performed for weaning purposes and these papers indicate the inherent weakness of heterogeneous
for airway protection for patients requiring prolonged ventila- patient populations and the use of case series and nonrandom-
tion. There are two major techniques for tracheostomy, open ized studies in meta-analyses [7173]. It is likely that expe-
and percutaneous, with various modifications of each. The dif- rience and technical modifications allow both the techniques
ferent surgical tracheostomy techniques are well described in to be performed in appropriate patients with the same de-
the references for this chapter [5962]. gree of safety and efficiency (<1% procedure-related mortality)
[74].
Other factors have been used to justify the use of one pro-
Open Surgical Tracheostomy cedure over the other such as cost efficiency [75,76], bleeding,
infection, procedural time, and estimated time from the deci-
In OST the patients neck is extended and the surgical field sion to proceed to successful completion of the procedure [74].
is exposed from the chin to several inches below the clavicle. Each factor can be used to justify one procedure over another,
This area is prepped and draped, and prophylactic antibiotics but it is likely that institutional practice variations and operator
are administered at the discretion of the surgeon. A vertical or experience are more important in the selection of one proce-
horizontal incision may be used; however, a horizontal incision dure over another. This is particularly relevant with respect to
will provide a better cosmetic result. The platysma muscle is the target population where ICU daily expenses far outweigh
divided in line with the incision and the strap muscles are sep- the procedural costs of either technique [77], and the expected
arated in the midline. The thyroid isthmus is then mobilized patient mortality can reach as high as 35% [78].
superiorly or divided as needed to access the trachea. In the It is probably more important to judiciously use the institu-
event of a low-lying cricoid cartilage, dissection on the ante- tional resources and the operator experience in providing the
rior wall of the trachea helps to mobilize the trachea out of best tracheal technique for these compromised patients. It is
the mediastinum, and also the use of a cricoid hook will ele- possible that the target population may vary from one institu-
vate the trachea to expose the second or third tracheal ring. tion to another (cardiac vs. trauma vs. neurosurgical vs. medi-
Following identification of the second or third tracheal ring, a cal ICU patients), which may influence the decision to perform
vertical tracheostomy is created or a tracheal flap (Bjork flap) one technique over another. Patient body habitus also plays a
is fashioned to create a fistulous tract by suturing the tracheal large role in selection: difficulty palpating tracheal rings in a
mucosal flap to the skin in the incision. short, thick-necked patient makes percutaneous tracheostomy
Variations on this technique include the use of retention not only difficult but dangerous. This patient is better served in
sutures through the lateral aspect of the tracheal walls for re- an operating room setting where optimum sedation/paralysis
traction purposes during tracheostomy tube insertion and for (if needed) and positioning can be accomplished while directly
expeditious reinsertion of a tracheostomy tube in the event of exposing the anterior trachea, mobilizing it if necessary to ac-
accidental tube decannulation [61,63]. cess the airway with an appropriately sized, sometimes custom-
made, tube.
Nonetheless, there are certain distinct advantages of PDT
Percutaneous Dilational Techniques that can be outlined as follows: (a) easier access for timing
of the procedure; (b) reduced operating room and manpower
The PDT are divided into several techniques; however, all are utilization; (c) less expensive than OST (even if both the pro-
alike in that they depend on the basic technique of guidewire cedures are performed in the ICU); (d) no requirement for
placement through the anterior tracheal wall, followed by di- transportation of critically ill patients to an operating room;
lation over this guidewire to create a tracheal stoma. This (e) improved cosmetic result; and (f) possibly reduced stomal
is all accomplished with provision of adequate monitoring infection, bleeding, and reduced tracheal secretions in the
of O2 saturations as well as adequate monitoring of cardiac parastomal area due to the tight fitting of the stoma around
rhythm and blood pressure. To be assured of early successful the tracheostomy tube.
tracheal cannulation within the operating room, use end-tidal We do recommend considering performing OST instead of
CO2 monitoring via the fresh tracheostomy tube and in the PST in the following patients: (a) patients with more severe res-
ICU by capnography [64]. There are several different modifica- piratory distress (FIO2 >0.60, positive end-expiratory pressure
tions from the original technique that was described by Ciaglia >10, and complicated translaryngeal intubation or a nonpal-
et al. [65] in 1988. There modifications are described in details pable cricoid cartilage or a cricoid cartilage <3 cm above the
elsewhere [62]. sternal notch [75]); (b) obese patients with abundant pretra-
Both techniques, PDT and OST, can be performed in either cheal subcutaneous fat; (c) patients with large goiters; (d) ab-
the ICU or the operating room. There have been several meta- normal airways secondary to congenital-acquired conditions;
analyses comparing OST with PDT, most showing no signifi- (e) the need for the constant attendance of a second physician
cant difference in mortality or major complications between to monitor ventilation or circulatory abnormalities; (f) abnor-
the two methods of performing the tracheostomy. Freeman mal bleeding diathesis that cannot be adequately corrected by
et al. [66] reviewed multiple prospective controlled studies pub- coagulation factors [79].
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110 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

tube that is lined with silicone and does not require an inner
TUBES AND CANNULAS cannula. In other tracheotomy tubes, inner cannulas serve to
extend the life of the tracheostomy tubes by preventing the
Characteristics of a good tracheostomy tube are flexibility to buildup secretions within the tracheostomy. The inner cannu-
accommodate varying patient anatomies, inert material, wide las can be easily removed and either cleaned or replaced with a
internal diameter, the smallest external diameter possible, a sterile, disposable one. Disposable inner cannulas have the ad-
smooth surface to allow easy insertion and removal, and suf- vantage of quick and efficient changing, a decrease in nursing
ficient length to be secured once placed, but not so long as time, decreased risk of cross-contamination, and guaranteed
to impinge the carina or other tracheal parts [80]. Until the sterility [87]. The obturator should be kept at the bedside at
late 1960s, when surgeons began to experiment with silicone all times in the event that reinsertion of the tracheostomy is
and other synthetic materials, tracheostomy tubes and cannu- necessary.
las were made of metal. At present, almost all tracheostomy
tubes are made of synthetic material. One disadvantage of a
silicone tube over a metal one is the increased thickness of the
tube wall, resulting in a larger outer diameter. Silicone tubes Humidification
are available with or without a cuff. The cuff allows occlusion
of the airway around the tube, which is necessary for positive- One of the functions of the upper airway is to moisten and hu-
pressure ventilation. It may also minimize aspiration. In the midify inspired air. Because tracheostomies bypass the upper
past, cuffs were associated with a fairly high incidence of tra- airway, it is vital to provide patients who have tracheostomies
cheal stenosis caused by ischemia and necrosis of the mucus with warm, humidified air. Humidification of inspired gases
membrane and subsequent cicatricial contracture at the cuff prevents complications in patients with tracheostomies. Fail-
site [81,82]. High-volume, low-pressure cuffs diminish pres- ure to humidify the inspired gases can obstruct the tube by
sure on the wall of the trachea, thereby minimizing (but not inspissated secretions, impair mucociliary clearance, and de-
eliminating) problems due to focal areas of pressure necrosis crease cough [88].
[83]. Cuff pressures should always be maintained at less than
30 cm H2 O, as higher pressures impair mucosal capillary blood
flow leading to ischemic injury to the trachea [84]. Cuff pres-
sures should be checked with a manometer daily in critically Suctioning
ill patients. Once the patient is weaned from mechanical ven-
tilation, the cuff should be deflated or consideration should be Patients with tracheostomies frequently have increased
given to placing an uncuffed tracheostomy tube until the pa- amounts of airway secretions coupled with decreased ability
tient can be decannulated. If the only purpose of the tube is to to clear them effectively. Keeping the airways clear of excess
secure the airway (sleep apnea) or provide access for suctioning secretions is important in decreasing the risk of lung infection
secretions, a tube without a cuff can be placed. A comprehen- and airway plugging [86]. Suctioning is frequently required
sive review of tracheostomy tubes can be found elsewhere [85]. in patients with poor or ineffective cough. Suction techniques
should remove the maximal amount of secretions while causing
the least amount of airway trauma [89]. Routine suctioning,
however, is not recommended [90]. In the patient who requires
POSTOPERATIVE CARE frequent suctioning because of secretions, who otherwise ap-
pears well, without infection and without tracheitis, the tube
The care of a tracheostomy tube after surgery is important.
itself may be the culprit. Downsizing the tube or even a short
Highlighted below are some specific issues that all intensivists
trial (while being monitored) with the tube removed may result
need to know when caring for patients with tracheostomies.
in significantly less secretions, obviating the need for the tube.

Wound and Dressing Care


Tracheostomy Tube Changes
Daily examinations of the stoma are important in identifying
infections or excoriations of the skin at the tracheostomy site Tracheostomy tubes do not require routine changing. In fact,
[86]. In addition, keeping the wound clean and free of blood there may be significant risks associated with routine tra-
and secretions is very important, especially in the immedi- cheostomy tube changes, especially if this is performed within a
ate posttracheostomy period. Dressing changes should be pre- week of the initial procedure and by inexperienced caregivers.
formed at least twice a day and when the dressings are soiled. A survey of accredited otolaryngology training programs sug-
Some authors recommend cleaning the stoma with 1:1 mixture gested a significant incidence of loss of airway and deaths as-
of hydrogen peroxide and sterile saline [86]. When changing sociated with routine changing of tracheostomy tubes within
dressings and tapes, special care is needed to avoid acciden- 7 days of initial placement, especially if they are changed by
tal dislodging of the tracheostomy tube. Sutures, placed either inexperienced physicians [91]. In general, the tube needs to
for fixation and/or through the rings themselves for exposure, be changed only under the following conditions: (a) there is a
should be removed as soon as practical, usually after 1 week functional problem with it, such as an air leak in the balloon;
when an adequate stoma has formed, to facilitate cleaning the (b) when the lumen is narrowed due to the buildup of dried
stomal area. Malodorous tracheal stomatitis that can lead secretions; (c) when switching to a new type of tube; or (d)
to an enlarging stoma around the tube should be treated with when downsizing the tube prior to decannulation. Ideally, a
topical antimicrobial dressings such as 0.25% Dakins solution tracheostomy tube should not be changed until 7 to 10 days
to facilitate resolution. after its initial placement. The reason for this is to allow the
tracheal stoma and the tract to mature. Patients who have their
tracheostomy tube changed before the tract is fully mature risk
Inner Cannulas having the tube misplaced into the soft tissue of the neck. If
the tracheostomy tube needs to be replaced before the tract has
The inner cannulas should be used at all times in most tra- had time to mature, the tube should be changed over a guide,
cheostomy tubes in the ICU. Bivona now makes a tracheostomy such as a suction catheter or tube changer [92].
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Chapter 12: Tracheostomy 111

studied 73 patients who received tracheostomies, who were


Oral Feeding and Swallowing Dysfunction without neurologic injury, and who were transferred from the
Associated with Tracheostomies ICU to the general ward [110]. Thirty-five of these patients
were decannulated prior to transfer to the wards. The decannu-
Great caution should be exercised before initiating oral feed- lated group had a significantly lower mortality. Factors found
ings in patients with tracheostomy. Numerous studies have to be associated with increased mortality in patients not de-
demonstrated that patients are at a significantly increased risk cannulated prior to transfer include body mass index greater
for aspiration when a tracheostomy is in place. than 30 kg per m2 and tenacious secretions.
Physiologically, patients with tracheostomies are more likely Patients with tracheostomies who are transferred to the gen-
to aspirate because the tracheostomy tube tethers the lar- eral medical wards do need special attention. We suggest that
ynx, preventing its normal upward movement needed to as- these patients be safely cared for on the general ward, provided
sist in glottic closure and cricopharyngeal relaxation [93]. there is a multidisciplinary team approach between physicians,
Tracheostomy tubes also disrupt normal swallowing by com- nurses, and respiratory therapist.
pressing the esophagus and interfering with deglutition [94],
decreasing duration of vocal cord closure [95], and resulting in
uncoordinated laryngeal closure [96]. In addition, prolonged
orotracheal intubation can result in prolonged swallowing dis-
COMPLICATIONS
orders even after the endotracheal tube is converted to a tra- Tracheostomies, whether inserted by percutaneous dilatation
cheostomy [97]. It is therefore not surprising that more than or open surgical procedure, are associated with a variety of
65% of patients with tracheostomies aspirate when swallow- complications. These complications are best grouped by the
ing [98,99]. It is felt that 77% of the episodes are clinically time of occurrence after the placement and are divided into
silent [100,101]. immediate, intermediate, and late complications (Table 12.4).
Before attempting oral feedings in a patient with a tra- The reported incidence of complications varies from as low
cheostomy, several objective criteria must be met. Obviously,
the patient must be consistently alert, appropriate, and able
to follow complex commands. The patient should also have
adequate cough and swallowing reflexes, adequate oral mo- TA B L E 1 2 . 4
tor strength, and a significant respiratory reserve [102]. These
criteria are probably best assessed by a certified speech ther- COMPLICATIONS OF TRACHEOSTOMIES [13]
apist. However, bedside clinical assessment may only identify
34% of the patients at high risk for aspiration [103]. Augment- Immediate complications (024 h)
ing the bedside swallowing evaluation by coloring feedings or Tube displacement
measuring the glucose in tracheal secretions does not appear Arrhythmia
to increase the sensitivity in detecting the risk of aspiration Hypotension
[104,105]. A video barium swallow may identify between 50% Hypoxia/hypercapnia
and 80% of patients with tracheostomies, who are at a high Loss of airway control
risk, to aspirate oral feeding [101,103]. A laryngoscopy to ob- Pneumothorax
serve directly a patients swallowing mechanics, coupled with Pneumomediastinum
a video barium swallow, may be more sensitive in predicting Acute surgical emphysema
which patients are at risk for aspiration [103]. Scintigraphic Major hemorrhage
studies may be the most sensitive test to determining which Bacteremia
patients are aspirating [106], and it is much easier to perform Esophageal injury (uncommon)
than endoscopy. Plugging of the tracheostomy [106] or using a Cardiorespiratory arrest (uncommon)
PassyMuir valve [107] may reduce aspiration in patients with Tracheolaryngeal injury (uncommon)
tracheostomies who are taking oral feedings, but this is not a Crushed airway from dilational tracheostomy (uncommon)
universal finding [108]. Intermediate complications (from day 1 to day 7)
Because of the high risk for aspiration and the difficulty Persistent bleeding
assessing which patients are at high risk to aspirate, we do Tube displacement
not institute oral feedings in our patients with tracheostomy in Tube obstruction (mucus, blood)
the ICU. We believe that the potential risks of a percutaneous Major atelectasis
endoscopically placed gastrostomy feeding tube or maintain- Wound infection/cellulitis
ing a nasogastric feeding tube are much less than the risk of Late complications (>day 7)
aspiration of oral feedings and its complications (i.e., recur- Tracheoinnominate artery fistula
rent pneumonia, acute respiratory distress syndrome, and pro- Tracheomalacia
longed weaning). Tracheal stenosis
Necrosis and loss of anterior tracheal cartilage
Tracheoesophageal fistula
Discharging Patients with Tracheotomies Major aspiration
Chronic speech and swallowing deficits
from the ICU to the General Ward Tracheocutaneous fistula
Two relatively recent studies have raised concern about the Conlan AA, Kopec SE: Tracheostomy in the ICU. J Intensive Care
safety of patients, who have been weaned from mechanical Med 15:1, 2000.
ventilation, who are transferred from the ICU to the general Angel LF, Simpson CB: Comparison of surgical and percutaneous
hospital ward with the tracheostomy in place [109,110]. Fer- dilational tracheostomy. Clin Chest Med 24:423, 2003.
Epstein SK: Late complications of tracheostomy. Respir Care 50:542,
nandez et al. retrospectively showed an increased mortality in
2005.
patients with tracheostomy tubes versus those decannulated Durbin CG: Early complications of tracheostomy. Respir Care 50:511,
prior to transfer out of the ICU, especially among patients with 2005.
a poorer overall prognosis [109]. Martinez et al. prospectively
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112 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

as 4% [111] to as high as 39% [28], with reported mortality with swallowing and promote aspiration [120]. Reintubation
rates from 0.03% to 0.6% [70,112]. Complication rates ap- of a tracheostomy can be accomplished by using a smaller,
pear to decrease with increasing experience of the physician beveled endotracheal tube and then applying a tracheostomy
performing the procedure [113]. Posttracheostomy mortality tube over the smaller tube, using the Seldinger technique [121].
and morbidity is usually due to iatrogenic tracheal laceration Using a nasogastric tube as a guidewire has also been described
[114], hemorrhage, tube dislodgment, infection, or obstruc- [92].
tion. Neurosurgical patients have a higher posttracheostomy If a tracheostomy becomes dislodged within 7 to 10 days of
complication rate than other patients [115,116]. Tracheostomy surgery, we recommend translaryngeal endotracheal intubation
is more hazardous in children than in adults, and carries special to establish a safe airway. The tracheostomy tube can then be
risks in the very young, often related to the experience of the replaced under less urgent conditions, with fiberoptic guidance
surgeon [117]. A comprehensive understanding of immediate, if needed.
intermediate, and late complications of tracheostomy and their
management is essential for the intensivist.
Subcutaneous Emphysema
Obstruction Approximately 5% of patients develop subcutaneous emphy-
sema after tracheostomy [121]. It is most likely to occur when
Obstruction of the tracheostomy tube is a potentially life- dissection is extensive and/or the wound is closed tightly. Par-
threatening complication. The tube may become plugged with tial closure of the skin wound is appropriate, but the underlying
clotted blood or inspissated secretions. In this case, the inner tissues should be allowed to approximate naturally. Subcuta-
cannula should be removed immediately and the patient suc- neous emphysema generally resolves over the 48 hours after
tioned. Should that fail, it may be necessary to remove the outer tracheostomy, but when the wound is closed tightly and the pa-
cannula also, a decision that must take into consideration the tient is coughing or on positive-pressure ventilation, pneumo-
reason the tube was placed and the length of time it has been in mediastinum, pneumopericardium, and/or tension pneumoth-
place. Obstruction may also be due to angulation of the distal orax may occur [118].
end of the tube against the anterior or posterior tracheal wall.
An undivided thyroid isthmus pressing against the angled tra-
cheostomy tube can force the tip against the anterior tracheal Pneumothorax and Pneumomediastinum
wall, whereas a low superior transverse skin edge can force
the tip of the tracheostomy tube against the posterior tracheal The cupola of the pleura extends well into the neck, especially
wall. An indication of this type of obstruction is an expiratory in patients with emphysema; thus, the pleura can be damaged
wheeze. Division of the thyroid isthmus and proper placement during tracheostomy. This complication is more common in
of transverse skin incisions prevent anterior or posterior tube the pediatric age group because the pleural dome extends more
angulation and obstruction [118]. cephalad in children [1]. The incidence of pneumothorax af-
ter tracheostomy ranges from 0% to 5% [1,111,121]. Many
surgeons routinely obtain a postoperative chest radiograph.
Tube Displacement/Dislodgment
Dislodgment of a tracheostomy tube that has been in place for Hemorrhage
2 weeks or longer is managed simply by replacing the tube. If it
cannot be immediately replaced or if it is replaced and the pa- Minor postoperative fresh tracheostomy bleeding occurs in up
tient cannot be ventilated (indicating that the tube is not in the to 37% of cases [1] and is probably the most common compli-
trachea), orotracheal intubation should be performed. Imme- cation of this procedure. Postoperative coughing and straining
diate postoperative displacement can be fatal if the tube cannot can cause venous bleeding by dislodging a clot or ligature. El-
be promptly replaced and the patient cannot be reintubated. evating the head of the bed, packing the wound, and/or using
Dislodgment in the early postoperative period is usually homeostatic materials usually controls minor bleeding. Major
caused by one of several technical problems. Failure to divide bleeding can occur in up to 5% of tracheotomies and is due
the thyroid isthmus may permit the intact isthmus to ride up to hemorrhage from the isthmus of the thyroid gland, loss of a
against the tracheostomy tube and thus displace it [118]. Exces- ligature from one of the anterior jugular veins, or injury to the
sively low placement of the stoma (i.e., below the second and transverse jugular vein that crosses the midline just above the
third rings) can occur when the thoracic trachea is brought jugular notch [122]. Persistent bleeding may require a return
into the neck by overextending the neck or by excessive trac- to the operating room for management. Techniques to decrease
tion on the trachea. When the normal anatomic relationships the likelihood of early posttracheostomy hemorrhage include
are restored, the trachea recedes below the suprasternal notch, (a) use of a vertical incision; (b) careful dissection in the mid-
causing the tube to be dislodged from the trachea [118,119]. line, with care to pick up each layer of tissue with instruments
The risk of dislodgment of the tracheostomy tube, a potentially rather than simply spread tissues apart; (c) liberal use of lig-
lethal complication, can be minimized by (a) transection of the atures rather than electrocautery; and (d) careful division and
thyroid isthmus at surgery, if indicated; (b) proper placement suture ligation of the thyroid isthmus. Late hemorrhage after
of the stoma; (c) avoidance of excessive neck hyperextension tracheostomy is usually due to bleeding granulation tissue or
and/or tracheal traction; (d) application of sufficiently tight another relatively minor cause. However, in these late cases, a
tracheostomy tube retention tapes; and (e) suture of the tra- tracheoinnominate artery fistula needs to be ruled out.
cheostomy tube flange to the skin in patients with short necks.
Some surgeons apply retaining sutures to the trachea for use
in the early postoperative period in case the tube becomes dis- Tracheoinnominate Artery Fistula
lodged, allowing the trachea to be pulled into the wound for
reintubation. Making a Bjork flap involves suturing the inferior At one point, it had been reported that 50% of all tracheostomy
edge of the trachea stoma to the skin, thus allowing a sure path- bleeding occurring more than 48 hours after the procedure was
way for tube placement. Bjork flaps, however, tend to interfere due to an often fatal complication of rupture of the innominate
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Chapter 12: Tracheostomy 113

artery caused by erosion of the tracheostomy tube at its tip of patients, more commonly in the pediatric age group. Early
or cuff into the vessel [121]. However, because the advent of postoperative fistula is a result of iatrogenic injury during the
the low-pressure cuff, the incidence of this complication has procedure [121,128]. The chances of creating a fistula can be
decreased considerably and occurs less than 1% of the time minimized by entering the trachea initially with a horizontal
[123]. incision between two tracheal rings (the second and third),
Eighty-five percent of tracheoinnominate fistulas occur thereby eliminating the initial cut into a hard cartilaginous
within the first month after tracheostomy [124], although they ring [118]. A late tracheoesophageal fistula may be due to tra-
have been reported as late as 7 months after operation. Other cheal necrosis caused by tube movement or angulation, as in
sites of delayed exsanguinating posttracheostomy hemorrhage neck hyperflexion, or excessive cuff pressure [119,121,128]. A
include the common carotid artery, superior and inferior thy- tracheoesophageal fistula should be suspected in patients with
roid arteries, aortic arch, and innominate vein [124]. Rupture cuff leaks, abdominal distention, recurrent aspiration pneu-
and fistula formation are caused by erosion through the tra- monia, and reflux of gastric fluids through the tracheostomy
chea into the artery due to excessive cuff pressure or by an- site. It may be demonstrated on endoscopy and contrast stud-
gulation of the tube tip against the anterior trachea. Infection ies. Tracheoesophageal fistulas require surgical repair. For pa-
and other factors that weaken local tissues, such as malnourish- tients who could not tolerate a major surgical procedure,
ment and steroids, also seem to play a role [125]. The innom- placement of an esophageal and a tracheal stent may be used
inate artery rises to about the level of the sixth ring anterior [130132].
to the trachea, and low placement of the stoma can also cre-
ate close proximity of the tube tip or cuff to the innominate
artery. Rarely, an anomaly of the innominate, occurring with Tracheal Stenosis
an incidence of 1% to 2% [124], is responsible for this disas-
trous complication. Pulsation of the tracheostomy tube is an Some degree of tracheal stenosis is seen in 40% to 60% of pa-
indication of potentially fatal positioning [124]. Initially, hem- tients with tracheostomies [112,133]. However, 3% to 12%
orrhage from a tracheoinnominate fistula is usually not exsan- of these stenoses are clinically significant enough to require in-
guinating. Herald bleeds must be investigated promptly using tervention [134]. Stenosis most commonly occurs at the level
fiberoptic tracheoscopy. If a tracheoinnominate fistula seems of the stoma or just above the stoma, but distal to the vocal
probable (minimal tracheitis, anterior pulsating erosions), the cords [127]. The stenosis typically results from bacterial in-
patient should be taken to the operating room for evaluation. fection or chondritis of the anterior and lateral tracheal walls.
Definitive management involves resection of the artery [126]. Granulation tissue usually develops first. Ultimately the gran-
The mortality rate approaches 100%, even with emergent sur- ulation tissue matures, becoming fibrous and covered with a
gical intervention [127]. Sudden exsanguinating hemorrhage layer of epithelium. The granulation tissue itself can also result
may be managed by hyperinflation of the tracheostomy cuff in other complications, such as obstructing the airway at the
tube or reintubation with an endotracheal tube through the level of the stoma, making changing the tracheostomy tube dif-
stoma, attempting to place the cuff at the level of the fistula. ficult, and occluding tube fenestrations. Identified risk factors
A lower neck incision with blind digital compression on the for developing tracheal stenosis include sepsis, stomal infec-
artery may be part of a critical resuscitative effort [128]. If a tra- tions, hypotension, advanced age, male gender, corticosteroid
cheoinnominate artery fistula is suspected, the patient should use, excess motion of the tracheostomy tube, oversized tube,
be evaluated in the operating room and preparations should be prolonged placement, elevated cuff pressures, and excessive ex-
made for a possible sternotomy. cision of the anterior trachea cartilage [127,135]. Using prop-
erly sized tracheostomy tubes, inflating cuffs only when indi-
cated, and maintaining intracuff pressures to less than 15 to
Misplacement of Tube 20 mm Hg may decrease the incidence of tracheal stenosis
[136]. Tracheal stenosis, as well as other long-term compli-
Misplacement of the tube error occurs at the time of surgery or cations, appears to be less with the percutaneous procedure
when the tube is changed or replaced through a fresh stoma. If [137139].
not recognized, associated mediastinal emphysema and tension Treatment options for granulation tissue include topical
pneumothorax can occur, along with alveolar hypoventilation. strategies (such as topical antibiotic or steroids, silver nitrate,
Injury to neurovascular structures, including the recurrent la- and polyurethane form dressings) or surgical strategies (laser
ryngeal nerve, is possible [119]. The patient must be orally in- excision, electrocautery, and surgical removal) [127]. Treat-
tubated or the tracheostoma recannulated. Some advise placing ment options for symptomatic tracheal stenosis include dilata-
retaining sutures in the trachea at the time of surgery. The avail- tion with a rigid bronchoscopy with coring, intralumen laser
ability of a tracheostomy set at the bedside after tracheostomy excision, or surgical resection with end-to-end tracheal anas-
facilitates emergency reintubation. tomosis [140].

Stomal Infections Tracheomalacia


An 8% to 12% incidence of cellulitis or purulent exudate is Tracheomalacia is a weakening of the tracheal wall resulting
reported with tracheostomy [1,121]. The risk of serious infec- from ischemic injury to the trachea, followed by chondritis,
tion is less than 0.5% [111]. Attention to the details of good then destruction, and necrosis of the tracheal cartilage [127].
stoma care and early use of antibiotics are advised. However, Consequently, there is collapse of the affected portion of the
prophylactic antibiotics are not recommended [129]. trachea with expiration, resulting in airflow limitation, air trap-
ping, and retention of airway secretions. Tracheomalacia may
ultimately result in the patient failing to wean from mechanical
Tracheoesophageal Fistula ventilation. A short-term therapeutic approach to tracheoma-
lacia is to place a longer tracheostomy tube to bypass the area
Tracheoesophageal fistula caused by injury to the posterior of malacia. Long-term treatment options include stenting, tra-
tracheal wall and cervical esophagus occurs in less than 1% cheal resection, or tracheoplasty [127].
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114 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

Dysphagia and Aspiration CONCLUSION


The major swallowing disorder associated with tracheostomy Tracheostomy is one of the most common surgical procedures
is aspiration (see the section Oral Feeding and Swallowing preformed in the ICU and appears to be the airway of choice
Dysfunction). Because of the high risk for aspiration, we do not for patients requiring mechanical ventilation for more than 1
recommend oral feeding in ICU patients with tracheostomies. to 2 weeks. The exact timing for converting patients to tra-
cheostomy is not entirely clear, so the physician must weight
the risks and benefits of tracheostomy versus translaryngeal
intubation and estimate the expected duration of mechanical
Tracheocutaneous Fistula ventilation for each individual patient. The physician perform-
ing the tracheostomy procedure needs to assess each patient to
Although the tracheostoma generally closes rapidly after de- determine the best technique (whether it be performed bedside
cannulation, a persistent fistula may occasionally remain, par- percutaneously or open in the operating room) for that specific
ticularly when the tracheostomy tube is present for a prolonged patient. The patients medical condition, the physicians expe-
period. If this complication occurs, the fistula tract can be ex- rience with the various techniques, and the hospitals resources
cised and the wound closed primarily under local anesthesia all need to be considered in determining the type of procedure
[141]. performed.

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P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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CHAPTER 13 GASTROINTESTINAL
ENDOSCOPY
ANUPAM SINGH, RANDALL S. PELLISH AND WAHID Y. WASSEF

Gastrointestinal (GI) endoscopy has evolved into an essential tients with hemodynamic instability or continuing transfusion
diagnostic and therapeutic tool for the treatment of critically requirements [2,3]. Urgent evaluation allows differentiation
ill patients in the new millennium. Innovations in the field con- between nonvariceal (peptic ulcer, esophagitis, MalloryWeiss
tinue to emerge. This chapter reviews general aspects of cur- tear, and angiodysplasia) and variceal lesions (esophageal or
rent indications and contraindications, provides an update of gastric varices), therefore promoting targeted therapy [4,5].
emerging technologies, and concludes by discussing potential Furthermore, urgent evaluation allows the identification and
future directions in the field. stratification of stigmata of bleeding, promoting appropriate
triage and risk stratification. Finally, urgent evaluation allows
the early identification of patients who may require surgical or
INDICATIONS radiologic intervention [6,7].
The indications for GI endoscopy in the intensive care unit Foreign Body Ingestions
(ICU) are summarized in Table 13.1 and are divided into those
for (a) evaluation of the upper GI tract (esophagus, stomach, Foreign body ingestions (FBI) can be divided into two groups:
and duodenum); (b) evaluation of the pancreaticobiliary tract; (i) food impactions and (ii) caustic ingestion. Food impactions
(c) evaluation of the mid-GI tract (jejunum and ileum); and (d) constitute the majority of FBI. Although most will pass spon-
evaluation of the lower GI tract (colon and rectum). taneously, endoscopic removal will be needed for 10% to 20%
of cases, and 1% of patients will ultimately require surgery [8].
Evaluation is crucial to determine the underlying cause of the
Evaluation of the Upper Gastrointestinal Tract obstruction (strictures, rings, and carcinoma). Although caus-
tic ingestions constitute only a small number of FBI, they are
Common indications for evaluation of the upper GI tract in the frequently life threatening, especially when they occur inten-
ICU include, but are not limited to, upper GI bleeding (UGIB), tionally in adults, and warrant endoscopic evaluation to prog-
caustic or foreign body ingestion, and placement of feeding nosticate and triage this group of patients [9].
tubes. Evaluation of the GI tract in ICU patients with clinically
insignificant bleeding or chronic GI complaints should gener- Feeding Tubes
ally be postponed until their medical/surgical illnesses improve.
One exception in this group of patients is if anticoagulation or Enteral nutrition improves outcomes in critically ill patients
thrombolytic therapy is being contemplated. and is preferred over parenteral nutrition in patients with a
functional GI tract [10]. Although nasoenteric and oroenteric
feeding tubes may be used for short-term enteral nutrition,
Upper Gastrointestinal Bleeding these tubes are felt to carry a higher risk of aspiration, dis-
With an estimated 300,000 admissions annually, acute UGIB placement, and sinus infections than endoscopically placed
is one of the most common medical emergencies [1]. It is de- percutaneous tubes. Percutaneous endoscopic gastrostomy
fined as the presence of melena, hematemesis, or blood in the (PEG) [11] is appropriate for most patients in the ICU when
nasogastric (NG) aspirate. Studies have shown improved out- there is a reversible disease process likely to require more
comes with urgent endoscopic management in critically ill pa- than 4 weeks of enteral nutrition (e.g., neurologic injury,
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 13: Gastrointestinal Endoscopy 117

TA B L E 1 3 . 1
INDICATIONS FOR GASTROINTESTINAL (GI)
ENDOSCOPY

Upper GI endoscopy
Upper GI bleeding (variceal or nonvariceal)
Caustic or foreign body ingestion
Placement of feeding or drainage tubes
Endoscopic retrograde cholangiopancreatography
Severe gallstone pancreatitis
Severe cholangitis
Bile leak
Lower GI endoscopy
Lower GI bleeding
Decompression of nontoxic megacolon or sigmoid volvulus
Unexplained diarrhea in the immunocompromised (graft
vs. host disease and cytomegalovirus infection) FIGURE 13.2. Tumor seen in proximal jejunum during double-
balloon enteroscopy (DBE). (Courtesy: David Cave, MD: Professor
of Medicine, University of Massachusetts Medical School.)
tracheostomy, and neoplasms of the upper aerodigestive tract)
[12]. PEG with jejunostomy tube and direct percutaneous en-
doscopic jejunostomy (PEJ) tubes are appropriate for select ing is the treatment of choice. When conventional ERCP is
patients in the ICU with high risk of aspiration. This includes unsuccessful, the recent introduction of miniature endoscopes
patients with severe gastroesophageal reflux disease and those (cholangioscopes or pancreatic scopes) with direct endoscopic
with gastroparesis. Enteral feeding beyond the ligament of Tre- visualization into these ductal systems has proved to be ben-
itz with a nasojejunal tube or a jejunostomy tube has been eficial through the use of advanced techniques such as elec-
demonstrated to be beneficial in patients with necrotizing pan- trohydraulic lithotripsy (EHL), laser lithotripsy, and glue [21].
creatitis. Occasionally, endoscopic gastrostomies or jejunos- Unfortunately, this technique is limited by its lack of availabil-
tomies may be indicated for decompression in patients with ity at all centers and the great deal of experience that is needed
GI obstruction [13]. Although these procedures are technically for its proper use.
simple and can be performed at the bedside under moderate
sedation, the risks and benefits should always be weighed care-
fully in this critically ill group of patients [14].
Evaluation of the Mid-Gastrointestinal Tract
(Jejunum and Ileum)
Evaluation of the Pancreaticobiliary Tract
Persistent, obscure GI bleeding is the most common indication
The indications for evaluation of the pancreaticobiliary tract for evaluation of this portion of the GI tract. Although this area
by endoscopic retrograde cholangiopancreatography (ERCP) of the GI tract had been difficult to evaluate in the past, this is
in critically ill patients are described in detail in Chapter 97 no longer the case. The advent of the wireless video capsule en-
and only briefly discussed here. Indications include biliary tract doscope (VCE), the double-balloon endoscope (DBE), and the
obstruction by gallstones [1517], pancreatic duct leaks, and spiral endoscope has made this area of the GI tract easily acces-
bile duct leaks (generally a postoperative or traumatic com- sible. VCE is usually the first test performed to look for possible
plication) [1820]. ERCP with sphincterotomy and/or stent- sites of bleeding in the jejunum and ileum (Fig. 13.1). If bleed-
ing or lesions are identified, the DBE (Fig. 13.2) or the spiral
endoscope (Fig. 13.3) would be used to implement therapy.

FIGURE 13.3. Bleeding seen in jejunum during spiral endoscopy.


FIGURE 13.1. Normal jejunal image as seen by video capsule endo- (Courtesy: David Cave, MD: Professor of Medicine, University of Mas-
scope (VCE). sachusetts Medical School.)
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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118 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

A B

FIGURE 13.4. A: X-ray showing cecal volvulus. (Courtesy: Milliam Kataoka, MD, Radiology Fellow,
UMass Memorial Medical Center.) B: CT scan showing cecal volvulus. (Courtesy: Milliam, MD, Radiology
Fellow, UMass Memorial Medical Center.)

gical conditions due to impaired colonic motility. Increasing


Evaluation of the Lower age, cecal diameter, delay in decompression, and status of the
Gastrointestinal Tract bowel significantly influence mortality, which is approximately
40% when ischemia or perforation is present. Evaluation of the
Colonoscopic evaluation is urgently needed in ICU patients markedly distended colon in the ICU setting involves exclud-
in cases of severe lower GI bleeding (LGIB), acute colonic ing mechanical obstruction and other causes of toxic mega-
distention, and at times for the evaluation of infection (Cy- colon, such as C. difficile infection, and assessing for signs of
tomegalovirus [CMV] and Clostridium difficile) in the im- ischemia and perforation. The risk of colonic perforation in
munocompromised patients [22,23]. acute colonic pseudo-obstruction increases when cecal diame-
Severe LGIB is predominantly a disease of the elderly. It ter exceeds 12 cm and when the distention has been present for
is defined as bleeding from a source distal to the ligament of greater than 6 days [30].
Treitz for less than 3 days [24]. Common causes include, but
are not limited to, diverticular bleeding, ischemic colitis, and
vascular abnormalities (arteriovenous malformations, AVMs).
However, as many as 11% of patients initially suspected to CONTRAINDICATIONS
have an LGIB are ultimately found to have a UGIB [25]. There-
fore, UGIB sources should always be considered first in patients Absolute and relative contraindications for endoscopic pro-
with LGIB, particularly in patients with unstable hemodynam- cedures are outlined in Table 13.2. In general, endoscopy is
ics. Once an upper GI source has been excluded, colonoscopy contraindicated when the patient is hemodynamically unsta-
should be performed to evaluate the lower GI tract and admin- ble, when there is suspected perforation, or when adequate pa-
ister appropriate therapy. Although urgent colonoscopy within tient cooperation or consent cannot be obtained [31]. However,
24 to 48 hours has shown to decrease the length of hospital stay there are exceptions to these rules. In these cases, resuscitation
[26] and endoscopic intervention is often successful, 80% to and endoscopic intervention would need to go on simultane-
85% of LGIBs stop spontaneously [27]. If the bleeding is severe ously.
or a source cannot be identified at colonoscopy, a technetium
(TC)-99m red blood cell scan with or without angiography
should be considered [28]. TA B L E 1 3 . 2
CONTRAINDICATIONS TO ENDOSCOPY
Acute Colonic Distention
This condition can be caused by acute colonic obstruction or Absolute contraindications
acute colonic pseudo-obstruction. Acute colonic obstruction Suspected or impending perforated viscus
can be caused by neoplasms, diverticular disease, and volvu- Risks to the patient outweigh benefits of the procedure
lus [29]. Volvulus (Fig. 13.4A and B) is a closed-loop ob- Relative contraindications
struction and is considered an emergency because unlike the Adequate patient cooperation or consent cannot be obtained
other causes of colonic obstruction, it can rapidly deteriorate Hemodynamic instability or myocardial infarction
from obstruction to ischemia, perforation, and death. How- Inadequate airway protection or hypoxemia
ever, if identified and treated early, it can be reversed. Acute Severe coagulopathy or thrombocytopenia
colonic pseudo-obstruction is a syndrome of massive dilation Inflammatory changes with increased risk of perforation
of the colon without mechanical obstruction that develops in (e.g., diverticulitis or severe inflammatory bowel disease)
hospitalized patients with serious underlying medical and sur-
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 13: Gastrointestinal Endoscopy 119

TA B L E 1 3 . 3
PERIPROCEDURAL CARE
ENDOSCOPIC METHODS FOR HEMOSTATIS
Key elements of planning interventional endoscopic proce-
dures include appropriate resuscitation and reversal of co- Thermal methods of hemostasis
agulopathies [32]. Proper sedation may simply involve light Heater probe
sedation in some patients [33]. However, in uncooperative, Multipolar electrocoagulation (bicap)
confused, or hypoxemic patients, it may require endotracheal Neodymium yttrium-aluminium-garnet (YAG) laser
intubation with deep sedation or general anesthesia. Although Argon plasma coagulation
endotracheal intubation does not significantly alter the risk of
Injection therapy for hemostasis
acquired pneumonia or cardiovascular events [33,34], it does
Distilled water or saline
generate controlled conditions during the procedure and may
Epinephrine (adrenaline)
help prevent massive aspiration (especially in patients with
Sclerosants (Cyanoacrylate, polidocanol, ethanol,
variceal bleeding). Antibiotics need to be considered in patients
ethanolamine oleare, sodium tetradecyl sulfate, sodium
with ascites and those with a history of endocarditis [35].
morrhuate)
Thrombin Fibrin-glue
Mechanical methods
Upper Gastrointestinal Endoscopy Clips
Band ligation
Upper Gastrointestinal Bleeding Detachable loops
In all patients with upper GI bleeding, an empty stomach is cru-
cial for thorough evaluation and identification of the bleeding
lesion. Through proper identification and treatment, studies
have shown a reduction in the risk of rebleeding and in the for hemostasis therapy (Fig. 13.5A and B). Controlled trials
need for surgical intervention [36]. Gastric lavage with an NG comparing clipping alone with other endoscopic hemostatic
tube or through use of the endoscope can clear the stomach techniques for nonvariceal UGIB are limited. Current evidence
of blood and clot partially. At times, the use of the prokinetic suggests that the hemoclip is not superior to other endoscopic
agents such as erythromycin (250 mg in 50 mL of normal saline modalities in terms of initial hemostasis, rebleeding rate, emer-
IV, 20 minutes prior to the procedure) may also be helpful. gency surgery, and the mortality rate for treatment of peptic
Studies have in fact shown that this approach may improve ulcer bleed [41]. However, they may be especially useful in the
the endoscopic visualization, improve the outcome, and de- treatment of critically ill patients [42] and patients with coag-
crease the need for second-look endoscopy [37]. Although ulopathy. Argon plasma coagulation (APC) is a noncoaptive
metoclopramide may theoretically have a similar effect, the technique that provides cautery to tissues by means of ionized
use of this agent has not been studied extensively. If a variceal argon gas. This method is most commonly used in the treat-
hemorrhage is suspected, on the basis of a clinical history or ment of AVMs. The YAG laser has fallen out of favor in the
physical examination suggesting portal hypertension, adjunc- acute management of high-risk patients because of its poor
tive therapy should be initiated immediately in the absence of portability and associated high cost.
contraindications. Both somatostatin analogues (octreotide) or Whatever method of hemostasis is used, patients with non-
vasopressin and its analogues have been used intravenously variceal UGIB need to be placed on antisecretory therapy with
(IV) to reduce portal pressures and prevent recurrent bleeding. a proton pump inhibitor (PPI) following endoscopic hemosta-
A recent meta-analysis slightly favored octreotide over terli- sis [2,40]. IV administration of a PPI is a faster way to achieve
pressin/vasopressin in the control of esophageal variceal bleed- gastric acid suppression than is oral administration of the same
ing [38]. Octreotide is usually given as a onetime bolus of 50 agent. Peak suppression after IV administration occurs within
to 100 g IV, followed by 25 to 50 g IV per hour for 3 to hours, compared with several days later after oral administra-
5 days. In addition, prophylactic antibiotics should be given to tion. This is crucial because it can reduce the risk of rebleeding
patients with active esophageal variceal bleeding for the pre- and the need for surgery [43,44]. The PPIs currently approved
vention of bacterial infections [39]. In contrast to nonvariceal for IV use in the United States include pantoprazole, lansopra-
hemorrhage, volume resuscitation should be performed judi- zole, and esomeprazole [45].
ciously in variceal bleeding as volume repletion can theoreti- If the bleeding is found to be caused by esophageal varices,
cally increase portal pressures. endoscopic variceal ligation (EVL) has become the procedure
If the bleeding source is found to be a peptic ulcer, the in- of choice [46]. With this technique, the varix is suctioned into
tervention will depend on the specific endoscopic findings [7]. a banding device attached to the tip of the endoscope and a
If an actively bleeding or a nonbleeding visible vessel is iden- rubber band is then deployed at its base to obliterate the varix.
tified in the crater of the ulcer, endoscopic hemostatic tech- In contrast, endoscopic sclerotherapy (EST) causes obliteration
niques are recommended. If the ulcer has a clean base with no by injection of a sclerosing agent (e.g., sodium morrhuate) in or
signs of active bleeding, endoscopic intervention is not indi- around the bleeding varix. A meta-analysis by Laine and Cook
cated. A number of endoscopic methods have been developed [47] suggested that EVL was superior to EST in all major out-
for hemostasis, including injection therapy, thermal cautery comes (recurrent bleeding, local complications such as ulcers
therapy, and mechanical hemostasis with clips (Table 13.3). or strictures, time to variceal obliteration, and survival). How-
The combination of injection therapy with thermal coaptive ever, EST is effective in controlling active bleeding in more than
therapy is superior to either alone [1,40]. Although no sin- 90% of cases and can be injected even with poor visualization
gle solution for endoscopic injection therapy appears superior during an active bleed.
to another, an epinephrinesaline solution is usually injected in Endoscopic methods (EST, EVL, and injection of fibrin glue)
four quadrants surrounding the lesion. Heater probe and multi- have also been used for the treatment of bleeding gastric varices
polar electrocoagulation instruments are subsequently applied in small and mostly uncontrolled studies. However, these meth-
with firm pressure to achieve optimal coaptation. Mechanical ods carry a considerable risk of rebleeding and mortality. Pa-
hemostasis, with hemoclips, has been a more recent addition tients with bleeding gastric varices generally require urgent
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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120 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

A B

FIGURE 13.5. A: Postpolypectomy bleeding. B: Hemostasis by hemoclip for postpolypectomy bleeding.

placement of a transjugular intrahepatic portosystemic shunt colon distention. This will establish the presence or absence of
(TIPS) [48]. mechanical obstruction. Subsequently, the patient should un-
dergo resuscitation with IV fluids (IVF), frequent reposition-
Enteric Feeding Tubes ing, NG and rectal tube placement, correction of metabolic
imbalances, and discontinuation of medications known to slow
Please see Chapter 16 for more detail on the placement of intestinal transit [50]. If conservative measures are unsuccess-
enteric feeding tubes. ful, decompressive endoscopy with minimal inflation of air re-
solves acute obstruction of the colon in the majority of cases
(81%) [51]. Despite a high recurrence rate (23% to 57%),
Pancreaticobiliary Endoscopy colonoscopy is often considered the initial procedure of choice
(Refer to Chapter 97) in the absence of intestinal ischemia [52,53]. This may be re-
duced with the placement of a decompression tube beyond
Small Bowel Endoscopy the splenic flexure [54]. In patients with mechanical obstruc-
tion, self-expanding metallic stents (SEMS) can be placed with
The techniques are essentially the same as those for upper GI good outcome [55]. In patients with nonmechanical obstruc-
endoscopy. Please refer to that section for details. tion, medical therapy with the parasympathomimetic agent
neostigmine should be considered. On the basis of a double-
blind, placebo-controlled, randomized trial, the parasympath-
Lower Gastrointestinal Endoscopy omimetic agent neostigmine has been shown to reduce colonic
distention significantly, reduce recurrence, and cause minimal
Unlike any of the other types of endoscopies previously dis- risk [56]. This agent should only be given in the absence of
cussed, this is the only one requiring a preprocedure bowel contraindications and under close cardiorespiratory monitor-
preparation. In urgent situations, this can be done through a ing with atropine at the bedside. Percutaneous, endoscopic, or
technique known as a rapid purge. This technique is usually surgical cecostomy presents another alternative if the afore-
achieved by drinking 4 L or more polyethylene glycolbased mentioned interventions are unsuccessful.
solutions over a 2- to 3-hour period. Approximately one-third
of hospitalized patients require an NGT for this type of prepa-
ration [49]. Metoclopramide (10 mg IV 1), administered
prior to starting the preparation, may help to control nausea COMPLICATIONS
and promote gastric emptying [25].
Although major complications of endoscopic procedures are
Lower Gastrointestinal Bleeding infrequent, critically ill patients may be particularly sensitive
to adverse outcomes due to multiple comorbidities. Complica-
The endoscopic treatment options for LGIB are similar to those tions can be divided into two groups: (i) general complications
for UGIB (see earlier in the chapter) and should be based on and (ii) specific complications (Table 13.4).
the stigmata of bleeding that are identified. Hemostasis is usu-
ally approached through a combination approach of injection
therapy with clipping or coagulation therapy.
FUTURE DIRECTIONS
Decompressive Endoscopy With the start of the new millennium, rapid advances have
A water-soluble contrast enema or computed tomography (CT) been made in the development of new techniques [57]. Nat-
should be the initial procedure to perform in patients with acute ural orifice transluminal endoscopic surgery (NOTES) is such
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 13: Gastrointestinal Endoscopy 121

TA B L E 1 3 . 4 a technique. It involves the use of a natural orifice (such


as stomach, rectum, vagina, or urethra) for intraperitoneal
COMPLICATIONS OF ENDOSCOPY access to perform a variety of procedures in the retroperi-
toneum, such as liver biopsy, cystogastrostomy, appendectomy,
General complications cholecystectomy, nephrectomy, and tubal ligation. In the ICU
Complications of conscious sedation (cardiopulmonary, setting, this type of a procedure is being evaluated for a number
allergic, paradoxical reactions) of potential scenarios: (i) the evaluation of suspected abdomi-
Bleeding (e.g., treatment of lesions, sphincterotomy) nal sepsis and ischemia at the bedside [58]; (ii) the feasibility of
Perforation (caused by endoscope, accessories, or air transgastric mapping of the diaphragm and implantation of a
insufflation) percutaneous electrode for therapeutic diaphragmatic stimula-
Aspiration tion in difficult-to-wean ICU patients [59]; and (iii) direct J-tube
Myocardial ischemia placement in selected patients without the need for surgery.
Specific complications (examples) Whatever role NOTES will have in the future of the critical
Endoscopic retrograde cholangiopancreatography: care population, it is already changing how we approach a
Pancreatitis, cholangitis, perforation number of GI problems and will be a part of the ever-evolving
Sclerotherapy: Ulceration, mediastinitis management of the critically ill population in the future to ex-
Stenting procedures: Stent migration pedite and improve their care.

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CHAPTER 14 PARACENTESIS AND


DIAGNOSTIC PERITONEAL LAVAGE
LENA M. NAPOLITANO

Refractory ascites occurs in 10% of patients with cirrho-


ABDOMINAL PARACENTESIS sis and is associated with substantial morbidity and a 1-year
survival of less than 50% [5,6]. For patients with refractory
Indications ascites, transjugular intrahepatic portosystemic shunt (TIPS) is
superior to LVP for long-term control of ascites, but it is as-
Abdominal paracentesis is a simple procedure that can be easily sociated with greater encephalopathy risk and does not affect
performed at the bedside in the intensive care unit and may pro- mortality [7,8].
vide important diagnostic information or therapy in critically ill
patients with ascites. As a diagnostic intervention, abdominal
paracentesis with removal of 20 mL of peritoneal fluid is per- Techniques
formed to determine the etiology of the ascites or to ascertain
whether infection is present, as in spontaneous bacterial peri- Before abdominal paracentesis is initiated, a catheter must be
tonitis [1]. It can also be used in any clinical situation in which inserted to drain the urinary bladder, and correction of any
the analysis of a sample of peritoneal fluid might be useful in underlying coagulopathy or thrombocytopenia should be con-
ascertaining a diagnosis and guiding therapy. The evaluation of sidered. A consensus statement from the International Ascites
ascites should therefore include a diagnostic paracentesis with Club states that there are no data to support the correction
ascitic fluid analysis. of mild coagulopathy with blood products prior to therapeutic
As a therapeutic intervention, abdominal paracentesis is paracentesis, but caution is needed when severe thrombocy-
usually performed to drain large volumes of abdominal ascites, topenia is present [3]. The practice guideline from the Amer-
termed large-volume paracentesis (LVP), with removal of more ican Association for the Study of Liver Diseases states that
than 5 L of ascitic fluid [2]. Ascites is the most common presen- routine correction of prolonged prothrombin time or throm-
tation of decompensated cirrhosis, and its development heralds bocytopenia is not required when experienced personnel per-
a poor prognosis, with a 50% 2-year survival rate. Effective form paracentesis [9]. This has been confirmed in a study of
first-line therapy for ascites includes sodium restriction (2 g per 1,100 LVPs in 628 patients [10]. But in critically ill patients,
day), use of diuretics, and LVP. When tense or refractory as- there is still uncertainty as to the optimal platelet count and
cites is present, LVP is safe and effective, and has the advantage prothrombin time for the safe conduct of paracentesis.
of producing immediate relief from ascites and its associated The patient must next be positioned correctly. In critically ill
symptoms [3]. LVP can be palliative by diminishing abdominal patients, the procedure is performed in the supine position with
pain from distention or improving pulmonary function by al- the head of the bed elevated at 30 to 45 degrees. If the patient
lowing better diaphragmatic excursion in patients who have as- is clinically stable and therapeutic LVP is being performed, the
cites refractory to aggressive medical management. LVP is also patient can be placed in the sitting position, leaning slightly
used for percutaneous decompression of resuscitation-induced forward, to increase the total volume of ascites removed.
abdominal compartment syndrome related to the development The site for paracentesis on the anterior abdominal wall
of acute tense ascites [4]. is then chosen (Fig. 14.1). The preferred site is in the lower
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 14: Paracentesis and Diagnostic Peritoneal Lavage 123

TRANSVERSE SECTION
30 to 45

CORONAL SECTION

CRANIAL 3 Withdraw ascitic fluid for analysis.


CRANIAL
Ascitic fluid Ascitic fluid

Superior
epigastric artery

CAUDAL
Rectus abdominus
muscle

Inferior epigastric
artery 4 Remove needle and allow cutaneous
tissue to retract to original position.

CRANIAL
Possible sites of Needle tract
Bladder (empty) needle insertion

Ascitic fluid

2 Insert needle
1 Stretch skin 1 to 2 cm
caudad to insertion site. CAUDAL
CAUDAL

FIGURE 14.1. Suggested sites for paracentesis.

abdomen, just lateral to the rectus abdominis muscle and in- ance. Diagnostic paracentesis usually requires 20 to 50 mL
ferior to the umbilicus. It is important to stay lateral to the peritoneal fluid and is commonly performed using the needle
rectus abdominis muscle to avoid injury to the inferior epigas- technique. However, if large volumes of peritoneal fluid are re-
tric artery and vein. In patients with chronic cirrhosis and caput quired, the catheter technique is used because it is associated
medusae (engorged anterior abdominal wall veins), these visi- with a lower incidence of complications. LVP should always
ble vascular structures must be avoided. Injury to these veins be performed with the catheter technique. Ultrasound guid-
can cause significant bleeding because of the underlying por- ance can be helpful in diagnostic paracentesis using the needle
tal hypertension and may result in hemoperitoneum. The left technique or in LVP using the catheter technique.
lower quadrant of the abdominal wall is preferred over the right
lower quadrant for abdominal paracentesis because critically
ill patients often have cecal distention. The ideal site is there-
Needle Technique
fore in the left lower quadrant of the abdomen, lateral to the With the patient in the appropriate position and the access
rectus abdominis muscle in the midclavicular line and inferior site for paracentesis determined, the patients abdomen is pre-
to the umbilicus. It has also been determined that the left lower pared with 2% chlorhexidine and sterile aseptic technique is
quadrant is significantly thinner and the depth of ascites greater used. If necessary, intravenous sedation is administered to pre-
compared with the infraumbilical midline position, confirming vent the patient from moving excessively during the procedure
the left lower quadrant as the preferred location for paracen- (see Chapter 20). Local anesthesia, using 1% or 2% lidocaine
tesis [11]. with 1:200,000 epinephrine, is infiltrated into the site. A skin
If the patient had previous abdominal surgery limited to the wheal is created with the local anesthetic, using a short 25-
lower abdomen, it may be difficult to perform a paracentesis in or 27-gauge needle. Then, using a 22-gauge, 1.5-in. needle,
the lower abdomen and the upper abdomen may be chosen. The the local anesthetic is infiltrated into the subcutaneous tissues
point of entry, however, remains lateral to the rectus abdominis and anterior abdominal wall, with the needle perpendicular to
muscle in the midclavicular line. If there is concern that the the skin. Before the anterior abdominal wall and peritoneum
ascites is loculated because of a previous abdominal surgery or are infiltrated, the skin is pulled taut inferiorly, allowing the
peritonitis, abdominal paracentesis should be performed under peritoneal cavity to be entered at a different location than the
ultrasound guidance to prevent iatrogenic complications. skin entrance site, thereby decreasing the chance of ascitic leak.
Abdominal paracentesis can be performed by the needle This is known as the Z-track technique. While tension is main-
technique, by the catheter technique, or with ultrasound guid- tained inferiorly on the abdominal skin, the needle is advanced
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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124 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

through the abdominal wall fascia and peritoneum, and local fluid can be sent for smear and culture for acid-fast bacilli if
anesthetic is injected. Intermittent aspiration identifies when tuberculous peritonitis is in the differential diagnosis.
the peritoneal cavity is entered, with return of ascitic fluid
into the syringe. The needle is held securely in this position Catheter Technique
with the left hand, and the right hand is used to withdraw ap-
Positioning, use of aseptic technique, and local anesthetic infil-
proximately 20 to 50 mL ascitic fluid into the syringe for a
tration are the same as for the needle technique. A 22-gauge,
diagnostic paracentesis.
1.5-in. needle attached to a 10-mL syringe is used to docu-
Once adequate fluid is withdrawn, the needle and syringe
ment the free return of peritoneal fluid into the syringe at the
are withdrawn from the anterior abdominal wall and the para-
chosen site. This needle is removed from the peritoneal cavity
centesis site is covered with a sterile dressing. The needle is re-
and a catheter-over-needle assembly is used to gain access to
moved from the syringe, because it may be contaminated with
the peritoneal cavity. If the anterior abdominal wall is thin, an
skin organisms. A small amount of peritoneal fluid is sent in a
18- or 20-gauge Angiocath can be used as the catheter-over-
sterile container for Gram stain and 10 mL is inoculated into
needle assembly. If the anterior abdominal wall is quite thick,
blood culture bottles immediately at bedside for culture and
as in obese patients, it may be necessary to use a long (5.25-in.,
sensitivity. The remainder of the fluid is sent for appropriate
18- or 20-gauge) catheter-over-needle assembly or a percuta-
studies, which may include cytology, cell count and differential,
neous single- or multiple-lumen central venous catheter (18-
protein, specific gravity, amylase, pH, lactate dehydrogenase,
or 20-gauge) and gain access to the peritoneal cavity using the
bilirubin, triglycerides, and albumin. A serum to ascites albu-
Seldinger technique.
min gradient (SAAG) greater than 1.1 g per dL is indicative of
The peritoneal cavity is entered as for the needle technique.
portal hypertension and cirrhosis (Table 14.1) [12]. Peritoneal
The catheter-over-needle assembly is inserted perpendicular to
the anterior abdominal wall using the Z-track technique; once
peritoneal fluid returns into the syringe barrel, the catheter is
TA B L E 1 4 . 1 advanced over the needle, the needle is removed, and a 20-
or 50-mL syringe is connected to the catheter. The tip of the
ETIOLOGIES OF ASCITES BASED ON NORMAL OR catheter is now in the peritoneal cavity and can be left in place
DISEASED PERITONEUM AND SERUM TO ASCITES until the appropriate amount of peritoneal fluid is removed.
ALBUMIN GRADIENT (SAAG) This technique, rather than the needle technique, should be
used when LVP is performed, because complications (e.g., in-
Normal peritoneum testinal perforation) may occur if a needle is left in the peri-
Portal hypertension (SAAG > 1.1 g/dL) toneal space for an extended period.
Hepatic congestion When the Seldinger technique is used in patients with a large
Congestive heart failure anterior abdominal wall, access to the peritoneal cavity is ini-
Constrictive pericarditis tially gained with a needle or catheter-over-needle assembly. A
Tricuspid insufficiency guidewire is then inserted through the needle and an 18- or
BuddChiari syndrome 20-gauge single- or multiple-lumen central venous catheter is
threaded over the guidewire. It is very important to use the
Liver disease
Z-track method for the catheter technique to prevent develop-
Cirrhosis
ment of an ascitic leak, which may be difficult to control and
Alcoholic hepatitis
may predispose the patient to peritoneal infection.
Fulminant hepatic failure
Massive hepatic metastases
Ultrasound Guidance Technique
Hypoalbuminemia (SAAG < 1.1 g/dL)
Patients who have had previous abdominal surgery or peritoni-
Nephrotic syndrome
tis are predisposed to abdominal adhesions, and it may be quite
Protein-losing enteropathy
difficult to gain free access into the peritoneal cavity for di-
Severe malnutrition with anasarca
agnostic or therapeutic paracentesis. Ultrasound-guided para-
Miscellaneous conditions (SAAG < 1.1 g/dL) centesis can be very helpful in this population, and in patients
Chylous ascites where the traditional technique fails, by providing accurate lo-
Pancreatic ascites calization of the peritoneal fluid collection and determining the
Bile ascites best abdominal access site. This procedure can be performed
Nephrogenic ascites using the needle or catheter technique as described earlier in
Urine ascites the chapter, depending on the volume of peritoneal fluid to be
Ovarian disease drained. Once the fluid collection is localized by the ultrasound
Diseased peritoneum infections (SAAG < 1.1 g/dL) probe, the abdomen is prepared and draped in the usual ster-
Bacterial peritonitis ile fashion. A sterile sleeve can be placed over the ultrasound
Tuberculous peritonitis probe so that there is direct real-time ultrasound visualization
Fungal peritonitis of the needle or catheter as it enters the peritoneal cavity. The
HIV-associated peritonitis needle or catheter is thus directed to the area to be drained,
and the appropriate amount of peritoneal or ascitic fluid is re-
Malignant conditions moved. If continued drainage of a loculated peritoneal fluid
Peritoneal carcinomatosis collection is desired, the radiologist can place a chronic in-
Primary mesothelioma dwelling peritoneal catheter using a percutaneous guidewire
Pseudomyxoma peritonei technique (see Chapter 22).
Hepatocellular carcinoma The use of ultrasound guidance for drainage of loculated
Other rare conditions peritoneal fluid collections has markedly decreased the inci-
Familial Mediterranean fever dence of iatrogenic complications related to abdominal para-
Vasculitis centesis. If the radiologist does not identify loculated ascites on
Granulomatous peritonitis the initial ultrasound evaluation and documents a large amount
Eosinophilic peritonitis of peritoneal fluid that is free in the abdominal cavity, he or she
can then indicate the best access site by marking the anterior
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Chapter 14: Paracentesis and Diagnostic Peritoneal Lavage 125

abdominal wall with an indelible marker. The paracentesis can studies did not specifically examine prevention of PICD (de-
then be performed by the clinician and repeated whenever nec- fined by an increase in plasma renin activity or aldosterone
essary. This study can be performed at the bedside in the in- concentration), and some studies have determined that albu-
tensive care unit with a portable ultrasound unit. A video for min prevented PCID more effectively than synthetic plasma
the correct procedural technique for paracentesis is available expanders [15,16].
for review [13]. Randomized trials comparing terlipressin (a vasoconstric-
tor) with albumin in PICD in cirrhosis documented that both
terlipressin and albumin prevented paracentesis-induced renal
Complications impairment in these patients [17,18]. Terlipressin may be as
effective as intravenous albumin in preventing PICD in pa-
The most common complications related to abdominal para- tients with cirrhosis. Midodrine and octreotide in combina-
centesis are bleeding and persistent ascitic leak. Because most tion or alone have shown conflicting results for improving
patients in whom ascites have developed also have some com- systemic and renal hemodynamics and renal function in pa-
ponent of chronic liver disease with associated coagulopathy tients with cirrhosis-related complications, including the pre-
and thrombocytopenia, it is very important to consider correc- vention of PICD, and additional studies are warranted [19].
tion of any underlying coagulopathy before proceeding with LVP is only transiently therapeutic; the underlying chronic
abdominal paracentesis. In addition, it is very important to se- disease induces reaccumulation of the ascites. Percutaneous
lect an avascular access site on the anterior abdominal wall. placement of a tunneled catheter is a viable and safe technique
The Z-track technique is very helpful in minimizing persistent to consider in patients who have symptomatic malignant as-
ascitic leak and should always be used. Another complication cites that require frequent therapeutic paracentesis for relief of
associated with abdominal paracentesis is intestinal or urinary symptoms [20].
bladder perforation, with associated peritonitis and infection.
Intestinal injury is more common when the needle technique is
used. Because the needle is free in the peritoneal cavity, iatro- DIAGNOSTIC PERITONEAL
genic intestinal perforation may occur if the patient moves or
if intra-abdominal pressure increases with Valsalva maneuver
LAVAGE
or coughing. Urinary bladder injury is less common and un- Before the introduction of diagnostic peritoneal lavage (DPL)
derscores the importance of draining the urinary bladder with by Root et al. [21] in 1965, nonoperative evaluation of the in-
a catheter before the procedure. This injury is more common jured abdomen was limited to standard four-quadrant abdom-
when the abdominal access site is in the suprapubic location; inal paracentesis. Abdominal paracentesis for the evaluation
therefore, this access site is not recommended. Careful adher- of hemoperitoneum was associated with a high false-negative
ence to proper technique of paracentesis minimizes associated rate. This clinical suspicion was confirmed by Giacobine and
complications. Siler [22] in an experimental animal model of hemoperitoneum
In patients who have large-volume chronic abdominal as- documenting that a 500-mL blood volume in the peritoneal
cites, such as that secondary to hepatic cirrhosis or ovarian cavity yielded a positive paracentesis rate of only 78%. The
carcinoma, transient hypotension and paracentesis-induced cir- initial study by Root et al. [21] reported 100% accuracy in the
culatory dysfunction (PICD) may develop during LVP. PICD is identification of hemoperitoneum using 1-L peritoneal lavage
characterized by worsening hypotension and arterial vasodila- fluid. Many subsequent clinical studies confirmed these find-
tion, hyponatremia, azotemia, and an increase in plasma renin ings, with the largest series reported by Fischer et al. [23] in
activity. Evidence is accumulating that PICD is secondary to an 1978. They reviewed 2,586 cases of DPL and reported a false-
accentuation of an already established arteriolar vasodilation positive rate of 0.2%, false-negative rate of 1.2%, and overall
with multiple etiologies, including the dynamics of paracente- accuracy of 98.5%. Since its introduction in 1965, DPL has
sis (the rate of ascitic fluid extraction), release of nitric oxide been a cornerstone in the evaluation of hemoperitoneum due
from the vascular endothelium, and mechanical modifications to blunt and penetrating abdominal injuries. However, it is non-
due to abdominal decompression [14]. specific for determination of the type or extent of organ injury.
PICD is associated with increased mortality and may be pre- Recent advances have led to the use of ultrasound (focused
vented with the administration of plasma expanders. It is very assessment with sonography in trauma [FAST]; Fig. 14.2) and
important to obtain reliable peripheral or central venous access rapid helical computed tomography (CT) in the emergent eval-
in these patients so that fluid resuscitation can be performed uation of abdominal trauma and have significantly decreased
if PICD develops during the procedure. A study randomized the use of DPL in the evaluation of abdominal trauma to less
72 patients to receive albumin or saline after total paracen- than 1% [2426]. FAST has replaced DPL as the initial screen-
tesis [15]. The incidence of PICD was significantly higher in ing modality of choice for severe abdominal trauma in more
the saline group compared with the albumin group (33.3% vs. than 80% of North American centers surveyed [27] and FAST
11.4%, p = 0.03). However, no significant differences were is now taught in the Advanced Trauma Life Support course
found when less than 6 L of ascitic fluid was evacuated (6.7% [28]. Practice management guidelines from the Eastern Associ-
vs. 5.6%, p = 0.9). Significant increases in plasma renin activ- ation for the Surgery of Trauma recommend FAST be consid-
ity were found 24 hours and 6 days after paracentesis when ered the initial diagnostic modality to exclude hemoperitoneum
saline was used, whereas no changes were observed with albu- [29]. DPL remains a valuable adjunct to modern imaging tech-
min. Albumin was more effective than saline in the prevention niques in early trauma assessment, particularly in hemodynam-
of PICD, but it is not required when less than 6 L of ascitic fluid ically unstable patients with initial FAST examination that is
is evacuated. Therefore, the administration of albumin intra- negative or equivocal and in the assessment of potential hol-
venously (6 to 8 g per L of ascites removed) is recommended low visceral injury in blunt abdominal trauma [30]. Diagnostic
with LVP (>6 L). peritoneal aspiration, without a full lavage, has also been uti-
There have been nine prospective randomized controlled tri- lized successfully in these circumstances [31].
als (n = 806) on the use of plasma expanders for therapeutic
paracentesis [1]. In a recent systematic review, there was no
significant difference between therapeutic paracentesis with or Indications
without volume expansion with albumin, nor with nonalbumin
plasma expanders compared with albumin for hyponatremia, The primary indication for DPL is evaluation of blunt abdomi-
renal impairment, encephalopathy, or death. However, these nal trauma in patients with associated hypotension. If the initial
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126 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

F
F
S
L
K
K
F

A B

L
B
F

F V
V

C D A
FIGURE 14.2. The FAST examination.

FAST examination is positive for hemoperitoneum, surgical inal trauma [33]. A hemodynamically unstable patient with
intervention (laparotomy) is required. If the FAST examina- abdominal penetrating injury requires no further investigation
tion is negative or equivocal, DPL should be considered. If and immediate laparotomy should be undertaken. Instead, the
the patient is hemodynamically stable and can be transported role of DPL in the hemodynamically stable patient with pen-
safely, CT scan of the abdomen and pelvis is the diagnostic etrating abdominal injury is to identify hemoperitoneum and
method of choice. If the patient is hemodynamically unstable hollow viscus or diaphragmatic injury. DPL has also been rec-
or requires emergent surgical intervention for a craniotomy, ommended as the initial diagnostic study in stable patients with
thoracotomy, or vascular procedure, it is imperative to de- penetrating trauma to the back and flank, defining an RBC
termine whether there is a coexisting intraperitoneal source count greater than 1,000 per L as a positive test [34]. Imple-
of hemorrhage to prioritize treatment of life-threatening in- mentation of this protocol decreased the total celiotomy rate
juries. FAST or DPL can be used to diagnose hemoperitoneum from 100% to 24%, and the therapeutic celiotomy rate in-
in patients with multisystem injury, who require general anes- creased from 15% to 80%.
thesia for the treatment of associated traumatic injuries. Pa- DPL may prove to be useful in evaluation for possible peri-
tients with associated thoracic or pelvic injuries should also tonitis or ruptured viscus in patients with an altered level of
have definitive evaluation for abdominal trauma, and DPL consciousness but no evidence of traumatic injury. DPL can be
can be used in these individuals. DPL can also be used to considered in critically ill patients with sepsis to determine if
evaluate for traumatic hollow viscus injury, and a cell count intra-abdominal infection is the underlying source. When DPL
ratio (defined as the ratio between white blood cell (WBC) is used to evaluate intra-abdominal infection, a WBC count
and red blood cell (RBC) count in the lavage fluid divided by greater than 500 per L of lavage fluid is considered positive.
the ratio of the same parameters in the peripheral blood) less DPL can also serve a therapeutic role. It is very effective in
than or equal to 1 has a specificity of 97% and sensitivity of rewarming patients with significant hypothermia. It may po-
100% [32]. tentially be used therapeutically in pancreatitis, fecal peritoni-
DPL can also be used to evaluate penetrating abdominal tis, and bile pancreatitis, but multiple clinical studies have not
trauma; however, its role differs from that in blunt abdom- documented its efficacy in these cases.
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Chapter 14: Paracentesis and Diagnostic Peritoneal Lavage 127

DPL should not be performed in patients with clear signs of returns on aspiration through the catheter, peritoneal lavage is
significant abdominal trauma and hemoperitoneum associated performed using 1 L Ringers lactate solution or normal saline
with hemodynamic instability. These patients should undergo that has been previously warmed to prevent hypothermia. The
emergent celiotomy. Pregnancy is a relative contraindication fluid is instilled into the peritoneal cavity through the DPL
to DPL; it may be technically difficult to perform because of catheter; afterward, the peritoneal fluid is allowed to drain out
the gravid uterus and is associated with a higher risk of com- of the peritoneal cavity by gravity until the fluid return slows.
plications. Bedside ultrasound evaluation of the abdomen in A minimum of 250 mL lavage fluid is considered a represen-
the pregnant trauma patient is associated with least risk to the tative sample of the peritoneal fluid [36]. A sample is sent to
woman and to the fetus. An additional relative contraindica- the laboratory for determination of RBC count, WBC count,
tion to DPL is multiple previous abdominal surgeries. These amylase concentration, and presence of bile, bacteria, or par-
patients commonly have multiple abdominal adhesions, and it ticulate matter. When the lavage is completed, the catheter is
may be very difficult to gain access to the free peritoneal cavity. removed and a sterile dressing applied over the site. Suture ap-
If DPL is indicated, it must be performed by the open technique proximation of the skin edges is not necessary when the closed
to prevent iatrogenic complications such as intestinal injury. technique is used for DPL.

Semiclosed Technique
Techniques Local anesthetic is infiltrated in the area of the planned incision
and a 2- to 3-cm vertical incision made in the infraumbilical or
Three techniques can be used to perform DPL: (i) the closed supraumbilical area. The incision is continued sharply down
percutaneous technique, (ii) the semiclosed technique, and (iii) through the subcutaneous tissue and linea alba, and the peri-
the open technique. The closed percutaneous technique, intro- toneum is then visualized. Forceps, hemostats, or Allis clamps
duced by Lazarus and Nelson [35] in 1979, is easy to perform, are used to grasp the edges of the linea alba and elevate the
can be done rapidly, is associated with a low complication rate, fascial edges to prevent injury to the underlying abdominal
and is as accurate as the open technique. It should not be used structures. The DPL lavage catheter with a metal inner stylet
in patients who have had previous abdominal surgery or a his- is inserted through the closed peritoneum into the peritoneal
tory of abdominal adhesions. The open technique entails the cavity at a 45-degree angle to the anterior abdominal wall,
placement of the peritoneal lavage catheter into the peritoneal directed toward the pelvis. When the cathetermetal stylet as-
cavity under direct visualization. It is more time consuming sembly is in the peritoneal cavity, the DPL catheter is advanced
than the closed percutaneous technique. The semiclosed tech- into the pelvis and the metal stylet removed. A 10-mL syringe
nique requires a smaller incision than does the open technique is attached to the catheter, and aspiration is conducted as previ-
and uses a peritoneal lavage catheter with a metal stylet to gain ously described. When the lavage is completed, the fascia must
entrance into the peritoneal cavity. It has become less popular be reapproximated with sutures, the skin closed, and a sterile
as clinicians have become more familiar and skilled with the dressing applied.
LazarusNelson closed technique.
The patient is placed in the supine position for all three Open Technique
techniques. A catheter is placed into the urinary bladder and a
nasogastric tube is inserted into the stomach to prevent iatro- After the administration of appropriate local anesthetic, a ver-
genic bladder or gastric injury. The nasogastric tube is placed tical midline incision approximately 3 to 5 cm long is made.
on continuous suction for gastric decompression. The skin of This incision is commonly made in the infraumbilical location,
the anterior abdominal wall is prepared with 2% chlorhex- but in patients with presumed pelvic fractures or retroperi-
idine solution and sterilely draped, leaving the periumbilical toneal hematomas or in pregnant patients, a supraumbilical
area exposed. Standard aseptic technique is used throughout location is preferred. The vertical midline incision is carried
the procedure. Local anesthesia with 1% or 2% lidocaine with down through the skin, subcutaneous tissue, and linea alba
1:200,000 epinephrine is used as necessary throughout the pro- under direct vision. The linea alba is grasped on either side
cedure. The infraumbilical site is used unless there is clinical using forceps, hemostats, or Allis clamps, and the fascia is ele-
concern of possible pelvic fracture and retroperitoneal or pelvic vated to prevent injury to the underlying abdominal structures.
hematoma, in which case the supraumbilical site is optimal. The peritoneum is identified, and a small vertical peritoneal in-
cision is made to gain entrance into the peritoneal cavity. The
DPL catheter is then inserted into the peritoneal cavity under
Closed Percutaneous Technique direct visualization and advanced inferiorly toward the pelvis.
With the closed percutaneous technique, local anesthesia is in- It is inserted without the stylet or metal trocar. When in posi-
filtrated inferior to the umbilicus and a 5-mm skin incision is tion, a 10-mL syringe is attached for aspiration. If aspiration of
made just at the inferior umbilical edge. An 18-gauge needle the peritoneal cavity is negative (i.e., no gross blood returns),
is inserted through this incision and into the peritoneal cav- peritoneal lavage is performed, as described earlier in the chap-
ity, angled toward the pelvis at approximately a 45-degree an- ter. As in the semiclosed technique, the fascia and skin must be
gle with the skin. The penetration through the linea alba and reapproximated to prevent dehiscence or evisceration, or both.
then through the peritoneum is felt as two separate pops. A A prospective randomized study documented that the
J-tipped guidewire is passed through the needle and into the LazarusNelson technique of closed percutaneous DPL can
peritoneal cavity, again directing the wire toward the pelvis be performed faster than the open procedure [37]. The pro-
by maintaining the needle at a 45-degree angle to the skin. cedure times with the closed technique varied from 1 to 3 min-
The 18-gauge needle is then removed and the DPL catheter utes, compared with 5 to 24 minutes for the open technique. It
inserted over the guidewire into the peritoneal cavity, using a was documented that the closed percutaneous technique was
twisting motion and guided inferiorly toward the pelvis. The as accurate as the open procedure and was associated with a
guidewire is then removed, and a 10-mL syringe is attached to lower incidence of wound infections and complications. The
the catheter for aspiration. If free blood returns from the DPL closed percutaneous technique, using the Seldinger technique,
catheter before the syringe is attached or if gross blood returns should therefore be used initially in all patients except those
in the syringe barrel, hemoperitoneum has been documented, who have had previous abdominal surgery or in pregnant pa-
the catheter is removed, and the patient is quickly transported tients. This has been confirmed in a study of 2,501 DPLs
to the operating room for emergent celiotomy. If no gross blood performed over a 75-month period for blunt or penetrating
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128 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

abdominal trauma [38]. The majority (2,409, or 96%) were TA B L E 1 4 . 2


performed using the closed percutaneous technique, and 92
(4%) were done open because of pelvic fractures, previous INTERPRETATION OF DIAGNOSTIC PERITONEAL
scars, or pregnancy. Open DPL was less sensitive than closed LAVAGE RESULTS
DPL in patients who sustained blunt trauma (90% vs. 95%),
but slightly more sensitive in determining penetration (100% POSITIVE
vs. 96%). Overall, there were few (21, or 0.8%) complications, Nonpenetrating abdominal trauma
and the overall sensitivity, specificity, and accuracy were 95%, Immediate gross blood return via catheter
99%, and 98%, respectively, using an RBC count of 100,000 Immediate return of intestinal contents or food particles
per L in blunt trauma and 10,000 per L in penetrating Aspiration of 10 mL blood via catheter
trauma as the positive threshold. A meta-analysis concluded Return of lavage fluid via chest tube or urinary catheter
that the closed DPL technique is comparable to the standard Red blood cell (RBC) count >100,000/L
open DPL technique in terms of accuracy and major compli- White blood cell (WBC) count >500/L
cations, with the advantage of reduced performance time with Cell count ratio (defined as the ratio between WBC and
closed DPL, which is offset by increased technical difficulties RBC count in the lavage fluid divided by the ratio of the
and failures [39]. same parameters in the peripheral blood) 1
A DPL modification [40] that resulted in more rapid infu- Amylase >175 U/100 mL
sion and drainage of lavage fluid used cystoscopy irrigation Penetrating abdominal trauma
tubing for instillation and drainage of the lavage fluid, saving Immediate gross blood return via catheter
an average of 19 minutes per patient for the DPL completion. Immediate return of intestinal contents or food particles
This modification can be applied to the closed percutaneous or Aspiration of 10 mL blood via catheter
open DPL technique to decrease the procedure time in critically Return of lavage fluid via chest tube or Foley catheter
ill patients. RBC count used is variable, from >1,000/L to
>100,000/L
WBC count >500/L
Interpretation of Results Amylase >175 U/100 mL
NEGATIVE
The current guidelines for interpretation of positive and nega-
Nonpenetrating abdominal trauma
tive results of DPL are provided in Table 14.2. A positive result
RBC count <50,000/L
can be estimated by the inability to read newsprint or typewrit-
WBC count <100/L
ten print through the lavage fluid as it returns through clear
Cell count ratio (defined as the ratio between WBC and
plastic tubing. This test is not reliable, however, and a quan-
RBC count in the lavage fluid divided by the ratio of the
titative RBC count in a sample of the peritoneal lavage fluid
same parameters in the peripheral blood) <1
must be performed [41]. For patients with nonpenetrating ab-
Amylase <75 U/100 mL
dominal trauma, an RBC count greater than 100,000 per L
of lavage fluid is considered positive and requires emergent ce- Penetrating abdominal trauma
liotomy. Fewer than 50,000 RBCs per L is considered negative RBC count used is variable, from <1,000/L to
and RBC counts of 50,000 to 100,000 per L are considered <50,000/L
indeterminate. The guidelines for patients with penetrating ab- WBC count <100/L
dominal trauma are much less clear with clinical studies us- Amylase <75 U/100 mL
ing an RBC count of greater than 1,000 or 10,000 per L to
greater than 100,000 per L as the criterion for a positive DPL
in patients with penetrating thoracic or abdominal trauma. The
lower the threshold the more sensitive the test, but the higher approximately 30% in patients who sustained traumatic di-
the nontherapeutic laparotomy rate. aphragmatic rupture. In addition, DPL is insensitive in detect-
Determination of hollow viscus injury by DPL is much more ing subcapsular hematomas of the spleen or liver that are con-
difficult. A WBC count greater than 500 per L of lavage fluid tained, with no evidence of hemoperitoneum. Although DPL is
or an amylase concentration greater than 175 units per dL of now used in the evaluation of nontraumatic intra-abdominal
lavage fluid is usually considered positive. These studies, how- pathology, the criteria for positive lavage in these patients have
ever, are not as accurate as the use of RBC count in the lavage not yet been established. Additional clinical studies are needed.
fluid to determine the presence of hemoperitoneum. One study
in patients with blunt abdominal trauma determined that the
WBC count in lavage fluid has a positive predictive value of
only 23% and probably should not be used as an indicator Complications
of a positive DPL [42]. Other studies analyzed alkaline phos-
phatase levels in DPL fluid to determine if this assay is helpful Complications of DPL by the techniques described here in-
in the diagnosis of hollow viscus injuries [43,44], but the re- clude malposition of the lavage catheter, injury to the intra-
sults have been variable. A prospective study used a diagnostic abdominal organs or vessels, iatrogenic hemoperitoneum,
algorithm of initial abdominal ultrasound, followed by helical wound infection or dehiscence, evisceration, and possible un-
CT and subsequent DPL (if CT was suggestive of blunt bowel necessary laparotomy. DPL is a very valuable technique, how-
or mesenteric injury) using a cell count ratio (defined as the ever, and if it is performed carefully, with attention to detail,
ratio between WBC and RBC count in the lavage fluid divided these complications are minimized. In the largest series pub-
by the ratio of the same parameters in the peripheral blood) lished to date, with more than 2,500 DPLs performed, the com-
greater than or equal to 1 to determine the need for laparo- plications rate was 0.8% [38]. Wound infection, dehiscence,
tomy in patients with blunt abdominal injuries [45]. This pro- and evisceration are more common with the open technique;
posed algorithm had a high accuracy (100%) while requiring therefore, the closed percutaneous technique is recommended
the performance of DPL in only a few (2%) patients. in all patients who do not have a contraindication to this tech-
It must be stressed that DPL is not accurate for determi- nique. Knowledge of all techniques is necessary, however, be-
nation of retroperitoneal visceral injuries or diaphragmatic cause the choice of technique should be based on the individual
injuries [46]. The incidence of false-negative DPL results is patients presentation.
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Chapter 14: Paracentesis and Diagnostic Peritoneal Lavage 129

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93(4):801817, 2009. hand-held focused abdominal sonography for trauma (FAST) in blunt ab-
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Hepatology 38(1):258, 2003. tomography for the initial assessment of blunt abdominal trauma patients.
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6. Garcia-Tsao G, Lim JK, Members of Veterans Affairs Hepatitis C Resource Life Support for Doctors. 8th ed. Chicago, American College of Surgeons,
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8. Salerno F, Camma C, Enea M, et al: Transjugular intrahepatic portosystemic 31. Kuncir EJ, Velmahos GC: Diagnostic peritoneal aspirationthe foster child
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with albumin in the prevention of circulatory changes after the paracentesis 42. Soyka J, Martin M, Sloan E, et al: Diagnostic peritoneal lavage: is an isolated
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21. Root H, Hauser C, McKinley C, et al: Diagnostic peritoneal lavage. Surgery 1993.
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23. Fischer R, Beverlin B, Engrav L, et al: Diagnostic peritoneal lavage 14 years 46. Fischer RP, Freeman T: The inadequacy of peritoneal lavage in diagnosing
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P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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130 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

CHAPTER 15 GASTROESOPHAGEAL
BALLOON TAMPONADE FOR ACUTE
VARICEAL HEMORRHAGE
MARIE T. PAVINI AND JUAN CARLOS PUYANA

Gastroesophageal variceal hemorrhage is an acute and catas- surveillance, whereas secondary prophylaxis includes nitrates,
trophic complication that occurs in one-third to one-half of transjugular intrahepatic portosystemic shunt (TIPS), and sur-
patients with portal pressures greater than 12 mm Hg [1]. Be- gical shunt [3]. Management of acute variceal bleeding involves
cause proximal gastric varices and varices in the distal 5 cm multiple simultaneous and sequential modalities. Balloon tam-
of the esophagus lie in the superficial lamina propria, they ponade is considered a temporary bridge within these modal-
are more likely to bleed and respond to endoscopic treat- ities. Self-expanding metal stents as an alternative to balloon
ment [2]. Variceal rupture is likely a factor of size, wall thick- tamponade are currently under investigation [4].
ness, and portal pressure, and may be predicted by Child-Pugh Splanchnic vasoconstrictors such as somatostatin, oc-
class, red wale markings indicating epithelial thickness, and treotide, terlipressin (the only agent shown to decrease mortal-
variceal size [1]. Although urgent endoscopy, sclerotherapy, ity), or vasopressin (with nitrates to reduce cardiac side effects)
and band ligations are considered first-line treatments, bal- decrease portal blood flow and pressure, and should be ad-
loon tamponade remains a valuable intervention in the treat- ministered as soon as possible [57]. In fact, Pourriat et al. [8]
ment of bleeding esophageal varices. Balloon tamponade is advocate administration of octreotide by emergency medical
accomplished using a multilumen tube, approximately 1 m personnel before patient transfer to the hospital. Recombinant
in length, with esophageal and gastric cuffs that can be in- activated factor VII has been reported to achieve hemostasis
flated to compress esophageal varices and gastric submucosal in bleeding esophageal varices unresponsive to standard treat-
veins, thereby providing hemostasis through tamponade, while ment, and may also be considered [9]. Emergent therapeutic
incorporating aspiration ports for diagnostic and therapeutic endoscopy in conjunction with pharmacotherapy is more ef-
usage. fective than pharmacotherapy alone and is also performed as
soon as possible. Band ligation has a lower rate of rebleed-
ing and complications when compared with sclerotherapy, and
should be performed preferentially, provided visualization is
HISTORICAL DEVELOPMENT adequate to ligate varices successfully [3,10]. Tissue adhe-
sives such as polidocanol and cyanoacrylate delivered through
In 1930, Westphal described the use of an esophageal sound as an endoscope are being used and studied outside the United
a means of controlling variceal hemorrhage. In 1947, successful States.
control of hemorrhage by balloon tamponade was achieved by Balloon tamponade is performed to control massive variceal
attaching an inflatable latex bag to the end of a MillerAbbot hemorrhage, with the hope that band ligation or sclerother-
tube. In 1949, a two-balloon tube was described by Patton and apy and secondary prophylaxis will then be possible (Fig.
Johnson. A triple-lumen tube with gastric and esophageal bal- 15.1). If bleeding continues beyond these measures, TIPS
loons, as well as a port for gastric aspiration, was described [11] is considered. Shunt surgery [12] may be considered if
by Sengstaken and Blakemore in 1950. In 1955, Linton and TIPS is contraindicated. Other alternatives include percuta-
Nachlas engineered a tube with a larger gastric balloon capa- neous transhepatic embolization, emergent esophageal tran-
ble of compressing the submucosal veins in the cardia, thereby section with stapling [13], esophagogastric devascularization
minimizing flow to the esophageal veins, with suction ports with esophageal transection and splenectomy, and hepatic
above and below the balloon. The Minnesota tube was de- transplantation. If gastric varices are noted, therapeutic op-
scribed in 1968 as a modification of the SengstakenBlakemore tions include endoscopic administration of the tissue adhe-
tube, incorporating the esophageal suction port, which will be sive cyanoacrylate, TIPS, balloon-occluded retrograde transve-
described later. Several studies have published combined expe- nous obliteration [14], balloon-occluded endoscopic injection
rience with tubes such as the LintonNachlas tube; however, therapy [15], and devascularization with splenectomy, shunt
the techniques described here are limited to the use of the Min- surgery, and liver transplantation.
nesota and SengstakenBlakemore tubes.

ROLE OF BALLOON TAMPONADE INDICATIONS AND


IN THE MANAGEMENT OF CONTRAINDICATIONS
BLEEDING ESOPHAGEAL VARICES A Minnesota or SengstakenBlakemore tube is indicated in pa-
tients with a diagnosis of esophageal variceal hemorrhage, in
Treatment of portal hypertension to prevent variceal rupture which neither band ligation nor sclerotherapy is technically
includes primary and secondary prophylaxis. Primary prophy- possible, readily available, or has failed [16]. If at all possi-
laxis consists of beta-blockers, band ligation, and endoscopic ble, making an adequate anatomic diagnosis is critical before
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Chapter 15: Gastroesophageal Balloon Tamponade for Acute Variceal Hemorrhage 131

FIGURE 15.1. Management of esophageal


variceal hemorrhage. Dx, diagnosis; Rx,
therapy; TIPS, transjugular intrahepatic por-
tosystemic shunt.

any of these balloon tubes are inserted. Severe upper gastroin-


testinal bleeding attributed to esophageal varices in patients TECHNICAL AND PRACTICAL
with clinical evidence of chronic liver disease results from other
causes in up to 40% of cases. The observation of a white
CONSIDERATIONS
nipple sign (platelet plug) is indicative of a recent variceal
bleed. A balloon tube is contraindicated in patients with re- Airway Control
cent esophageal surgery or esophageal stricture [17]. Some au-
thors do not recommend balloon tamponade when a hiatal Endotracheal intubation (see Chapter 1) is imperative in pa-
hernia is present, but there are reports of successful hemor- tients with upper gastrointestinal bleeding and hemodynamic
rhage control in some of these patients [18]. If there is no other compromise, encephalopathy, or both. The incidence of as-
option, it may be practical to titrate to the lowest effective bal- piration pneumonia is directly related to the presence of en-
loon pressures especially if repeated endoscopic sclerotherapy cephalopathy or impaired mental status [20]. Suctioning of
has been performed as there is increased risk of esophageal pulmonary secretions and blood that accumulates in the hy-
perforation [19]. popharynx is facilitated in patients who have been intubated.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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132 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

Sedatives and analgesics are more readily administered in in- presence of infection [23]. Prophylactic antibiotic use reduces
tubated patients, and may be required often because balloon the incidence of early rebleeding and increases survival [24].
tamponade is poorly tolerated in most patients and retching or Intravenous proton pump inhibitors are more efficacious than
vomiting may lead to esophageal rupture [21]. The incidence histamine-2-receptor antagonists in maintaining gastric pH at
of pulmonary complications is significantly lower when endo- a goal of 7. Ulcers can form from sclerotherapy, banding, or
tracheal intubation is routinely used [22]. direct cuff pressure during balloon tamponade. Shaheen et al.
[25] found that the postbanding ulcers in patients receiving a
proton pump inhibitor were two times smaller than those in
Hypovolemia, Shock, and Coagulopathy patients who had not received a proton pump inhibitor.

Adequate intravenous access should be obtained with large-


bore venous catheters for blood product administration and
fluid resuscitation with crystalloids and colloids. A central ve- Balloons, Ports, and Preparation
nous catheter or pulmonary artery catheter may be required
to monitor intravascular filling pressures, especially in patients All lumens should be flushed to assure patency and the bal-
with severe cirrhosis, advanced age, or underlying cardiac and loons inflated underwater to check for leaks. Two clean 100-mL
pulmonary disease. Packed red blood cells should be adminis- (or larger) Foley-tip syringes and two to four rubber-shod
tered keeping four to six units available in case of severe recur- hemostats should be readied for inflation of the balloons. To
rent bleeding, which commonly occurs in these patients. Coag- ensure that the gastric balloon will not be positioned in the
ulopathies, thrombocytopenia, or qualitative platelet disorders esophagus, preinsertion compliance should be tested by plac-
should be treated emergently. Octreotide and other vasocon- ing 100-mL aliquots of air up to the listed maximum recom-
strictive therapies should be initiated as indicated. mended volumes into the gastric inflation port while recording
the corresponding pressures using a manometer attached to the
gastric pressure port. In this way, postinsertion pressures can be
Clots and Gastric Decompression compared. A portable handheld manometer allows for simpler
continuous monitoring as well as patient transport and repo-
If time permits, placement of an Ewald tube and aggressive sitioning. If possible, a second manometer should be attached
lavage and suctioning of the stomach and duodenum facilitates to the esophageal pressure port to facilitate inflation and con-
endoscopy, diminishes the risk of aspiration, and may help con- tinuous monitoring. Place a plug or hemostat on the other arm
trol hemorrhage from causes other than esophageal varices. It of the esophageal inflation port instead of a 100-mL syringe
should be removed prior to balloon tamponade. as the manometer may also be used for inflation, rendering the
syringe superfluous [26,27]. Both balloons are then completely
deflated using suction and clamped with rubber hemostats or
Infection and Ulceration plugged before lubrication. The Minnesota tube (Fig. 15.2)
enjoys a fourth lumen that allows for suctioning above the
Mortality is increased if infection is present in bleeding cirrhotic esophageal balloon [18], whereas the SengstakenBlakemore
patients. The rate of early rebleeding is also increased in the tube (Fig. 15.3) must have a 14 to 18 French nasogastric tube

FIGURE 15.2. Minnesota tube.


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Chapter 15: Gastroesophageal Balloon Tamponade for Acute Variceal Hemorrhage 133

FIGURE 15.3. SengstakenBlakemore tube.

secured a few centimeters proximal to the esophageal balloon this stage suggests esophageal placement [27,35]. A (portable)
to be used for esophageal decompression. The nasogastric tube radiograph must be obtained that includes the upper abdomen
should be used even if the esophageal balloon is not inflated be- and lower chest (Figs. 15.4 and 15.5). When it is documented
cause inflation of the gastric balloon precludes proper drainage that the gastric balloon is below the diaphragm, it should be
of esophageal secretions [28]. If the patient is to be placed in further inflated with air in 100 mL aliquots to a volume of
an aircraft (i.e., for evacuation), water should be instilled into 250 to 300 mL. The gastric balloon of the Minnesota tube can
balloon(s) instead of air [29]. be inflated to 450 to 500 mL. If the change in manometric
pressure for an aliquot is more than 15 mm Hg of the preinser-
tion pressure or if the gastric balloon is underinflated causing
upward migration, erroneous esophageal placement should be
Insertion and Placement of the Tube considered. Record tube insertion depth (i.e., at the teeth). Tube
balloon inlets should be clamped with rubber-shod hemostats
The head of the bed should be elevated to reduce the risk of as- after insufflation. Hemorrhage is frequently controlled with
piration. Oral suction should be readied and the correct length insufflation of the gastric balloon alone without applying trac-
of the tube to reach the patients stomach should be selected tion, but in patients with torrential hemorrhage, it is necessary
(usually 45 to 60 cm orally). If the patient is not intubated, head to apply traction (vide infra). If the bleeding continues, the
down with left lateral positioning should be attained to mini- manometer attached to the esophageal pressure port is used to
mize the risk of aspiration [17]. If using a Minnesota tube, the inflate the esophageal balloon to a pressure of approximately
esophageal aspiration port should be set to continuous suc- 45 mm Hg. Some authors inflate the esophageal balloon in all
tion and the tube generously lubricated with lidocaine jelly patients immediately after insertion. If there is still bleeding,
prior to inserting it through the nose or mouth into the stom- deflate the esophageal balloon, apply more traction, and rein-
ach. However, the nasal route is not recommended in patients flate in the event that it is a gastric variceal bleed. Pressures
with coagulopathy or thrombocytopenia. In the difficult in- should be monitored and maintained.
sertion, the tube may be placed endoscopically [30] or with
a guidewire [31]. Duarte described a technique of placing the
tube in a longitudinally split Ewald tube [32]. Auscultation in
the epigastrium while air is injected through the gastric lumen
verifies the position of the tube, but the position of the gas- Fixation and Traction Techniques
tric balloon must be confirmed at this time radiologically or
by ultrasound if it is more expedient [33] as high placement Fixation and traction on the tube depend on the route of in-
can lead to esophageal rupture and low placement to duodenal sertion. When the nasal route is used, attachment of a sponge
rupture [34]. The manometer is then connected to the gastric rubber cuff around the tube at the nostril prevents skin and
pressure port and the gastric balloon is inflated with no more cartilage necrosis. When traction is required, the tube should
than 80 mL of air. A pressure of greater than 15 mm Hg at be attached to a cord that is passed over a catchers mask for
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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134 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

inserted through the mouth, traction is better applied by plac-


ing a football helmet on the patient and attaching the tube to
the face mask of the helmet after a similar weight is applied
for tension. Pressure sores can occur on the head and forehead
if the helmet does not fit properly or if it is used for a pro-
longed period. Several authors recommend overhead traction
for either oral or nasal insertion [37].

Maintenance, Monitoring, and Care


Periodically flush ports to ensure patency. To reduce en-
cephalopathy, the gastric aspiration port should be used to thor-
oughly lavage the stomach before being set to low intermittent
suction. It may be used later for medication administration.
The esophageal port may be set to intermittent or continuous
suction, depending on the extent of bleeding and drainage [35].
Tautness and inflation should be checked often and at least 1
hour after insertion, allowing for only transient fluctuations of
as much as 30 mm Hg with respirations and esophageal spasm.
Sedation or a pressure decrease may be necessary if large pres-
sure fluctuations persist. If repositioning of the tube is required,
assure that the esophageal balloon is deflated. Soft restraints
should also be in use and the head of the bed elevated. The
FIGURE 15.4. Proper positioning of the Minnesota tube. tube is left in place a minimum of 24 hours with gastric balloon
tamponade maintained continuously for up to 48 hours. The
esophageal balloon should be deflated for 5 minutes every 6
hours to help prevent mucosal ischemia and esophageal necro-
maximum transportability [36] or a pulley in a bed with an sis. Radiographic assurance of correct placement should be ob-
overhead orthopedic frame and aligned directly as it comes tained every 24 hours and when dislodgement is suspected (Fig.
out of the nose to avoid contact with the nostril. This type of 15.5). Watch for localized cervical edema, which may signal ob-
system allows maintenance of traction with a known weight struction or malpositioning [38]. A pair of scissors should be
of 500 to 1,500 g either temporarily with IV fluid bags [17] kept with the apparatus in case rapid decompression becomes
or more permanently with block weights. When the tube is necessary as balloon migration can acutely obstruct the airway
or rupture the esophagus. It is advisable to take care not to
utilize bare hemostats and to clamp at the thicker portion of
the ports as it is possible for the lumen to become obliterated
and the tube thus impacted [39].

FIGURE 15.5. Radiograph showing correct position of the tube; the


gastric balloon is seen below the diaphragm. Note the Salem sump FIGURE 15.6. Chest radiograph showing distal segment of the tube
above the gastric balloon and adjacent to the tube. (Courtesy: Ashley coiled in the chest and the gastric balloon inflated above the diaphragm
Davidoff, MD.) in the esophagus. (Courtesy: Ashley Davidoff, MD.)
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Chapter 15: Gastroesophageal Balloon Tamponade for Acute Variceal Hemorrhage 135

ulopathy, presence of shock, Glasgow Coma Score, and total


Removal of the Tube volume of sclerosing agent (ethanolamine).
Aspiration pneumonia is the most common complication of
Once hemorrhage is controlled, the esophageal balloon is de- balloon tamponade. The severity and fatality rate is related to
flated first. This may be done incrementally over time if de- the presence of impaired mental status and encephalopathy in
sired. The gastric balloon is left inflated for an additional 24 patients with poor control of the airway. The incidence ranges
to 48 hours and may be deflated if there is no evidence of from 0% to 12%. Acute laryngeal obstruction and tracheal
bleeding. The tube is left in place 24 hours longer. If bleed- rupture are the most severe of all complications and the worst
ing recurs, the balloon is reinflated. The tube is removed if no examples of tube migration or malpositioning. Migration of the
further bleeding occurs. Primary therapy and secondary pro- tube occurs when the gastric balloon is not inflated properly
phylaxis, as described previously, should be considered because after adequate positioning in the stomach or when excessive
balloon tamponade is a bridge intervention and rebleeding can traction (>1.5 kg) is used, causing migration cephalad to the
occur in up to two thirds of patients within 3 months without esophagus or hypopharynx. Mucosal ulceration of the gastroe-
therapy [3]. sophageal junction is common and is directly related to pro-
longed traction time (>36 hours). Perforation of the esophagus
is reported as a result of misplacing the gastric balloon above
COMPLICATIONS the diaphragm (Fig. 15.6). The incidence of complications that
are a direct cause of death ranges from 0% to 20%.
Rebleeding when the cuff(s) is deflated should be anticipated.
The highest risk of rebleeding is in the first few days after bal-
loon deflation. By 6 weeks, the risk of rebleeding returns to ACKNOWLEDGMENTS
premorbid risk level. Independent predictors of mortality in
patients undergoing balloon tamponade, described by Lee et The authors thank Claire LaForce (Rutland Regional Medical
al. [40], include blood transfusion greater than 10 units, coag- Center, Rutland, VT) for her help in collecting references.

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from esophageal varices. Clin Gastroenterol Hepatol 2:78, 2004. associated risk with balloon tamponade after endoscopic therapy. Myth or
10. Avgerinos A, Armonis A, Manolakpoulos S, et al: Endoscopic sclerother- reality? Hepatogastroenterology 53:536539, 2006.
apy versus variceal ligation in the long-term management of patients with 30. Lin TC, Bilir BM, Powis ME: Endoscopic placement of Sengstaken-
cirrhosis after variceal bleeding: a prospective randomized study. J Hepatol Blakemore tube. J Clin Gastroenterol 31(1):2932, 2000.
26:1034, 1997. 31. Wilcox G, Marlow J: A special maneuver for passage of the Sengstaken-
11. Banares R, Casado M, Rodriquez-Laiz JM, et al: Urgent transjugular in- Blakemore tube. Gastrointest Endosc 30(6):377, 1984.
trahepatic portosystemic shunt for control of acute variceal bleeding. Am J 32. Duarte B: Technique for the placement of the Sengstaken-Blakemore tube.
Gastroenterol 93:75, 1998. Surg Gynecol Obstet 168(5):449450, 1989.
12. Lewis JJ, Basson MD, Modlin IM: Surgical therapy of acute esophageal 33. Lock G, Reng M, Messman H, et al: Inflation and positioning of the gas-
variceal hemorrhage. Dig Dis Sci 10[Suppl 1]:46, 1992. tric balloon of a Sengstaken-Blakemore tube under ultrasonographic control.
13. Mathur SK, Shah SR, Soonawala ZF, et al: Transabdominal extensive oe- Gastrointest Endosc 45(6):538, 1997.
sophagogastric devascularization with gastro-oesophageal stapling in the 34. Kandel G, Gray R, Mackenzie RL, et al: Duodenal perforation by a Linton-
management of acute variceal bleeding. Br J Surg 84:413, 1997. Nachlas balloon tube. Am J Gastroenterol 83(4):442444, 1988.
14. Kitamoto M, Imamura M, Kamada K, et al: Balloon-occluded retrograde 35. Isaacs K, Levinson S: Insertion of the Minnesota tube, in Drossman D (ed):
transvenous obliteration of gastric fundal varices with hemorrhage. AJR Am Manual of Gastroenterologic Procedures. 3rd ed. New York, Raven Press,
J Roentgenol 178:1167, 2002. 1993, pp 2735.
15. Shiba M, Higuchi K, Nakamura K, et al: Efficacy and safety of balloon- 36. Kashiwagi H, Shikano S, Yamamoto O, et al: Technique for positioning the
occluded endoscopic injection sclerotherapy as a prophylactic treatment for Sengstaken-Blakemore tube as comfortably as possible. Surg Gynecol Obstet
high-risk gastric fundal varices: a prospective, randomized, comparative clin- 172(1):63, 1991.
ical trial. Gastrointest Endosc 56:522, 2002. 37. Hunt PS, Korman MG, Hansky J, et al: An 8-year prospective experience with
16. Burnett DA, Rikkers LF: Nonoperative emergency treatment of variceal hem- balloon tamponade in emergency control of bleeding esophageal varices. Dig
orrhage. Surg Clin North Am 70:291, 1990. Dis Sci 27:413, 1982.
17. McCormick PA, Burroughs AK, McIntyre N: How to insert a Sengstaken- 38. Juffe A, Tellez G, Eguaras M, et al: Unusual complication of the Sengstaken-
Blakemore tube. Br J Hosp Med 43:274, 1990. Blakemore tube. Gastroenterology 72(4, Pt 1):724725, 1977.
18. Minocha A, Richards RJ: Sengstaken-Blakemore tube for control of massive 39. Bhasin DK, Zargar SA, Mandal M, et al: Endoscopic removal of impacted
bleeding from gastric varices in hiatal hernia. J Clin Gastroenterol 14:36, Sengstaken-Blakemore tube. Surg Endosc 3(1):5455, 1989.
1992. 40. Lee H, Hawker FH, Selby W, et al: Intensive care treatment of patients with
19. Chong CF: Esophageal rupture due to Sengstaken-Blakemore tube misplace- bleeding esophageal varices: results, predictors of mortality, and predictors
ment. World J Gastroenterol 11(41):65636565, 2005. of the adult respiratory distress syndrome. Crit Care Med 20:1555, 1992.
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136 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

CHAPTER 16 ENDOSCOPIC PLACEMENT


OF FEEDING TUBES
LENA M. NAPOLITANO

ing is not recommended in patients with severe malabsorption


INDICATIONS FOR or early in the course of severe short-gut syndrome.
ENTERAL FEEDING
Nutritional support is an essential component of intensive
care medicine (see Chapters 190192). It has become increas- ACCESS TO THE
ingly evident that nutritional support administered via the en- GASTROINTESTINAL TRACT
teral route is far superior to total parenteral nutrition [1
11]. The Society of Critical Care Medicine/American Society After deciding to provide enteral nutrition, the clinician must
for Parenteral and Enteral Nutrition Guidelines for the Pro- decide whether to deliver the formula into the stomach, duo-
vision and Assessment of Nutrition Support Therapy in the denum, or jejunum, and determine the optimal method for ac-
Adult Critically Ill Patient [1], the Canadian Clinical Practice cessing the site, which is based on the function of the patients
Guidelines for Nutrition Support in Critically Ill Adults [2], gastrointestinal tract, duration of enteral nutritional support
the European Society for Clinical Nutrition and Metabolism required, and risk of pulmonary aspiration. Gastric feeding
(ESPEN) Guidelines on Enteral Nutrition for Intensive Care provides the most normal route for enteral nutrition, but it is
[3], and the Practice Management Guidelines for Nutritional commonly poorly tolerated in the critically ill patient because
Support of the Trauma Patient [4] all strongly recommend of gastric dysmotility with delayed emptying [14]. Enteral nu-
that enteral nutrition be used in preference to parenteral trition infusion into the duodenum or jejunum may decrease the
nutrition. incidence of aspiration because of the protection afforded by
Provision of nutrition through the enteral route aids in pre- a competent pyloric sphincter; however, the risk of aspiration
vention of gastrointestinal mucosal atrophy, thereby maintain- is not completely eliminated by feeding distal to the pylorus
ing the integrity of the gastrointestinal mucosal barrier. Other [1517]. Infusion into the jejunum is associated with the low-
advantages of enteral nutrition are preservation of immuno- est risk of pulmonary aspiration. An advantage of this site of
logic gut function and normal gut flora, improved use of nutri- administration is that enteral feeding can be initiated early in
ents, and reduced cost. Some studies suggest that clinical out- the postoperative period, because postoperative ileus primar-
come is improved and infectious complications are decreased ily affects the colon and stomach and only rarely involves the
in patients who receive enteral nutrition compared with par- small intestine. However, the early use of postpyloric feeding
enteral nutrition. instead of gastric feeding in critically ill adult patients with no
An evidence-based consensus statement on the management evidence of impaired gastric emptying was not associated with
of critically ill patients with severe acute pancreatitis also rec- significant clinical benefits [18,19].
ommended that enteral nutrition be used in preference to par-
enteral nutrition [12]. A systematic review also concluded that
patients with severe acute pancreatitis should begin enteral
nutrition early because such therapy modulates the stress re- TECHNIQUES
sponse, promotes more rapid resolution of the disease process,
Enteral feeding tubes can be placed via the transnasal, transo-
and improves outcome [13].
ral, or percutaneous transgastric or transjejunal routes. If these
Although there are absolute or relative contraindications to
procedures are contraindicated or unsuccessful, the tube may
enteral feeding in selected cases, most critically ill patients can
be placed by endoscopy, using endoscopic and laparoscopic
receive some or all of their nutritional requirements via the gas-
technique, or surgically via a laparotomy [20].
trointestinal tract. Even when some component of nutritional
support must be provided intravenously (IV), feeding via the
gut is desirable.
Several developmentsincluding new techniques for place- Nasoenteric Route
ment of feeding tubes, availability of smaller caliber, minimally
reactive tubes, and an increasing range of enteral formulas Nasoenteric tubes are the most commonly used means of pro-
have expanded the ability to provide enteral nutritional support viding enteral nutritional support in critically ill patients. This
to critically ill patients. Enteral feeding at a site proximal to the route is preferred for short- to intermediate-term enteral sup-
pylorus may be absolutely or relatively contraindicated in pa- port when eventual resumption of oral feeding is anticipated.
tients with increased risk of pulmonary aspiration, but feeding It is possible to infuse enteral formulas into the stomach us-
more distally (particularly distal to the ligament of Treitz) de- ing a conventional 16- or 18-French (Fr) polyvinyl chloride
creases the likelihood of aspiration. Other relative or absolute nasogastric tube, but patients are usually much more comfort-
contraindications to enteral feeding include fistulas, intestinal able if a small-diameter silicone or polyurethane feeding tube
obstruction, upper gastrointestinal hemorrhage, and severe in- is used. Nasoenteric tubes vary in luminal diameter (6 to 14 Fr)
flammatory bowel disease or intestinal ischemia. Enteral feed- and length, depending on the desired location of the distal
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Chapter 16: Endoscopic Placement of Feeding Tubes 137

orifice: stomach, 30 to 36 in.; duodenum, 43 in.; jejunum, at


least 48 in. Some tubes have tungsten-weighted tips designed
to facilitate passage into the duodenum via normal peristalsis;
others have a stylet. Most are radiopaque. Some tubes per-
mit gastric decompression while delivering formula into the
jejunum.
Nasoenteric feeding tubes should be placed with the patient
in a semi-Fowlers or sitting position. The tip of the tube should
be lubricated, placed in the patients nose, and advanced to the
posterior pharynx. If the patient is alert and can follow in-
structions, the patient should be permitted to sip water as the
tube is slowly advanced into the stomach. To avoid uninten-
tional airway placement and serious complications, position
of the tube should be ascertained after it has been inserted to
30 cm. Acceptable means of documenting intraesophageal lo-
cation of the tube include a chest radiograph or lack of CO2
detection through the lumen of the tube by capnography or col-
orimetry. If the tube is in the airway, CO2 will be detected and
the tube must be removed. Alternatively, commercial systems
are now available to track tube progression from the esoph- FIGURE 16.1. Endoscopic placement of nasoenteral feeding tube. En-
agus through the stomach to the duodenum by electromag- doscopy forceps and gastroscope advance the feeding tube in the duo-
denum.
netic means. Proper final placement of the tube in the stomach
must be confirmed by chest or upper abdominal radiograph
before tube feeding is begun. The following methods to as-
sess final tube placement are unreliable and do not assess tube
misdirection into the lower respiratory tract: auscultation over inserted and advanced through the esophagus into the gas-
the left upper quadrant with air insufflation through the tube, tric lumen. An endoscopy forceps is passed through the biopsy
assessment of pH with gastric content aspiration, and easy pas- channel of the endoscope and used to grasp the tip of the enteral
sage of the tube to its full length with the absence of gagging feeding tube. The endoscope, along with the enteral feeding
and coughing [21,22]. The tube should be securely taped to the tube, is advanced distally into the duodenum as far as possible
nose, forehead, or cheek without tension. (Fig. 16.1).
Delayed gastric emptying has been confirmed in critically The endoscopy forceps and feeding tube remain in position
ill patients and may contribute to gastric feeding intolerance. in the distal duodenum as the endoscope is withdrawn back
One study randomized 80 critically ill patients to gastric feed- into the gastric lumen. The endoscopy forceps are opened, the
ing with erythromycin (200 mg IV every 8 hours as a prokinetic feeding tube released, and the endoscopy forceps withdrawn
agent) or through a transpyloric feeding tube and identified that carefully back into the stomach. On first pass, the feeding tube
the two were equivalent in achieving goal caloric requirements is usually lodged in the second portion of the duodenum. The
[23]. Spontaneous transpyloric passage of enteral feeding tubes portion of the feeding tube that is redundant in the stomach
in critically ill patients is commonly unsuccessful secondary to is advanced slowly into the duodenum using the endoscopy
the preponderance of gastric atony. The addition of a tungsten forceps to achieve a final position distal to the ligament of Tre-
weight to the end of enteral feeding tubes and the development itz (Fig. 16.2). An abdominal radiograph is obtained at the
of wire or metal stylets in enteral feeding tubes are aimed at im- completion of the procedure to document the final position of
proving the success rate for spontaneous transpyloric passage. the nasoenteral feeding tube. Endoscopic placement of postpy-
Once the tube is documented to be in the stomach, various bed- loric enteral feeding tubes is highly successful, eliminates the
side techniques including air insufflation, pH-assisted, magnet- risk of transporting the patient to the radiology department
guided [24], and spontaneous passage with [25] or without for fluoroscopic placement, and allows prompt achievement
motility agents may help to facilitate transpyloric feeding tube of nutritional goals because enteral feeding can be initiated
passage. immediately after the procedure.
IV metoclopramide and erythromycin have been recom- The recent development of ultrathin endoscopes (outer di-
mended as prokinetic agents. But a Cochrane Database System- ameter 5.1 to 5.9 mm vs. 9.8 mm in standard gastroscope) has
atic Review concluded that doses of 10 or 20 mg of IV meto- enabled nasoenteric feeding tube placement via transnasal en-
clopramide were equally ineffective in facilitating transpyloric doscopy using an over-the-wire technique. A 90% success rate
feeding tube placement [26]. No matter which techniques are was documented with endoscopic procedure duration of ap-
used to facilitate transpyloric passage of enteral feeding tubes, proximately 13 minutes, shorter than fluoroscopic procedure
these tubes must be inserted by skilled practitioners using de- duration and without the need for additional sedation [34].
fined techniques [27,28]. Unsedated transnasal ultrathin endoscopy can also be used for
If the tube does not pass into the duodenum on the first feeding tube or percutaneous endoscopic gastrostomy (PEG)
attempt, placement can be attempted under endoscopic assis- placement in patients who are unable to undergo transoral en-
tance or fluoroscopic or electromagnetic guidance. The lat- doscopy, that is, those who have partial or complete occlusion
ter method requires specialized equipment. Endoscopic place- of the mouth [35].
ment of nasoenteral feeding tubes is easily accomplished in Electromagnetic guidance employs a feeding tube with a
the critically ill patient and can be performed at the bedside guidewire that emits electromagnetic waves. A box with three
using portable equipment [2933]. Transnasal or transoral en- receivers that is placed on the patients xiphoid process trian-
doscopy can be used for placement of nasoenteral feeding tubes gulates the position of the tube. The clinician is able to view
in critically ill patients [33]. The patient is sedated appropri- the tip on a monitor as it passes down the esophagus through
ately (see Chapter 20), and topical anesthetic is applied to the stomach and into the duodenum. Although the manu-
the posterior pharynx with lidocaine or benzocaine spray. A facturer asserts an x-ray after the procedure is not necessary,
43- to 48-in.-long nasoenteric feeding tube with an inner wire the practice at many institutions is to obtain an x-ray to confirm
stylet is passed transnasally into the stomach. The endoscope is placement of the tube.
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138 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

is administered before the procedure. The fiberoptic gastro-


scope is inserted into the stomach, which is then insufflated
with air. The lights are dimmed, and the assistant applies digi-
tal pressure to the anterior abdominal wall in the left subcostal
area approximately 2 cm below the costal margin, looking for
the brightest transillumination (light reflex). The endoscopist
should be able to clearly identify the indentation in the stom-
ach created by the assistants digital pressure on the anterior
abdominal wall (digital reflex); otherwise, another site should
be chosen.
When the correct spot has been identified, the assistant anes-
thetizes the anterior abdominal wall. The endoscopist then in-
troduces a polypectomy snare through the endoscope. A small
incision is made in the skin, and the assistant introduces a
large-bore catheterneedle stylet assembly into the stomach and
through the snare. The snare is then tightened securely around
the catheter. The inner stylet is removed, and a looped inser-
tion wire is introduced through the catheter and into the stom-
ach. The cannula is slowly withdrawn so that the snare grasps
the wire. The gastroscope is then pulled out of the patients
mouth with the wire firmly grasped by the snare. The end of
the transgastric wire exiting the patients mouth is then tied to
a prepared gastrostomy tube. The assistant pulls on the end
of the wire exiting from the abdominal wall while the endo-
scopist guides the lubricated gastrostomy tube into the poste-
rior pharynx and the esophagus. With continued traction, the
gastrostomy tube is pulled into the stomach so that it exits on
the anterior abdominal wall. The gastroscope is reinserted into
the stomach to confirm adequate placement of the gastrostomy
tube against the gastric mucosa and to document that no bleed-
ing has occurred. The intraluminal portion of the tube should
contact the mucosa, but excessive tension on the tube should be
avoided because this can lead to ischemic necrosis of the gastric
wall. The tube is secured to the abdominal wall using sutures.
Feedings may be initiated immediately after the procedure or
FIGURE 16.2. Abdominal radiograph documenting the optimal po-
sition of an endoscopically placed nasoenteral feeding tube, past the 24 hours later.
ligament of Treitz.
Push Technique
The push technique is similar to the pull technique. The gas-
Percutaneous Route troscope is inserted and a point on the anterior abdominal wall
localized, as for the pull technique. Rather than introducing a
PEG tube placement, introduced by Ponsky et al. [36] in 1990, looped insertion wire, however, a straight guidewire is snared
has become the procedure of choice for patients requiring pro- and brought out through the patients mouth by withdraw-
longed enteral nutritional support. PEG tubes range in size ing the endoscope and snare together. A commercially devel-
from 20 to 28 Fr. PEG rapidly replaced open gastrostomy as the oped gastrostomy tube (SachsVine) with a tapered end is then
method of choice for enteral nutrition. Unlike surgical gastros- passed in an aboral direction over the wire, which is held taut.
tomy, PEG does not require general anesthesia and laparotomy The tube is grasped and pulled out the rest of the way. The
and eliminates the discomfort associated with chronic nasoen- gastroscope is reinserted to check the position and tension on
teric tubes. This procedure can be considered for patients who the tube.
have normal gastric emptying and low risk for pulmonary as-
piration, and can be performed in the operating room, in an Introducer Technique
endoscopy unit, or at the bedside in the intensive care unit with
portable endoscopy equipment. The introducer technique uses a peel-away introducer tech-
PEG should not be performed in patients with near or total nique originally developed for the placement of cardiac pace-
obstruction of the pharynx or esophagus, in the presence of makers and central venous catheters. The gastroscope is
coagulopathy, or when transillumination is inadequate. Rela- inserted into the stomach and an appropriate position for place-
tive contraindications are ascites, gastric cancer, and gastric ul- ment of the tube is identified. After infiltration of the skin with
cer. Previous abdominal surgery is not a contraindication. The local anesthetic, a 16- or 18-gauge needle is introduced into
original method for PEG was the pull technique; more recent the stomach. A J-tipped guidewire is inserted through the nee-
modifications are the push and introducer techniques. dle into the stomach and the needle is withdrawn. Using a
twisting motion, a 16-Fr introducer with a peel-away sheath
is passed over the guidewire into the gastric lumen [37,38].
Pull Technique The guidewire and introducer are removed, leaving in place
The pull technique is performed with the patient in the supine the sheath that allows placement of a 14-Fr Foley catheter. The
position. The abdomen is prepared and draped. The posterior sheath is peeled away after the balloon is inflated with 10 mL
pharynx is anesthetized with a topical spray or solution (e.g., of normal saline. Some advocate this as the optimal method
benzocaine spray or viscous lidocaine), and IV sedation (e.g., 1 for PEG in patients with head and neck cancer, related to an
to 2 mg of midazolam; see Chapter 20) is administered. A pro- overall lower rate of complications in this patient population
phylactic antibiotic, usually a first-generation cephalosporin, [39].
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Chapter 16: Endoscopic Placement of Feeding Tubes 139

Percutaneous Endoscopic Gastrostomy/Jejunostomy All percutaneous gastrostomy and jejunostomy procedures


described here have been established as safe and effective. The
If postpyloric feeding is desired (especially in patients at high
method is selected on the basis of the endoscopists experience
risk for pulmonary aspiration), a PEG/jejunostomy may be per-
and training and the patients nutritional needs.
formed. The tube allows simultaneous gastric decompression
and duodenal/jejunal enteral feeding [40]. A second, smaller
feeding tube can be attached and passed through the gastros-
tomy tube and advanced endoscopically into the duodenum or SURGICAL PROCEDURES
jejunum. When the PEG is in position, a guidewire is passed
Since the advent of PEG, surgical placement of enteral feed-
through it and grasped using endoscopy forceps. The guidewire
ing tubes is usually performed as a concomitant procedure as
and endoscope are passed into the duodenum as distally as pos-
the last phase of a laparotomy performed for another indica-
sible. The jejunal tube is then passed over the guidewire through
tion. Occasionally, an operation solely for tube placement is
the PEG into the distal duodenum, advanced into the jejunum,
performed in patients requiring permanent tube feedings when
and the endoscope is withdrawn. An alternative method is to
a percutaneous approach is contraindicated or unsuccessful. In
grasp a suture at the tip of the feeding tube or the distal tip of
these cases, the laparoscopic approach to enteral access should
the tube itself and pass the tube into the duodenum, using for-
be considered [48]. Laparoscopic gastrostomy was introduced
ceps advanced through the biopsy channel of the endoscope.
in 2000, 10 years after the PEG. Patients who are not candi-
This obviates the need to pass the gastroscope into the duo-
dates for PEG, due to head and neck cancer, esophageal ob-
denum, which may result in dislodgment of the tube when the
struction, large hiatal hernia, gastric volvulus, or overlying
endoscope is withdrawn.
intestine or liver, should be considered for laparoscopic gas-
trostomy or jejunostomy.
Direct Percutaneous Endoscopic Jejunostomy
Jejunostomy tubes can be placed endoscopically by means of a
PEG with jejunal extension (PEG-J) or by direct percutaneous Gastrostomy
jejunostomy (PEJ) [41,42]. Because the size of the jejunal ex-
tension of the PEG-J tube is significantly smaller than that of Gastrostomy is a simple procedure when performed as part
the direct PEJ, some have suggested that the PEJ provides more of another intra-abdominal operation. It should be considered
stable jejunal access for those who require long-term jejunal when prolonged enteral nutritional support is anticipated after
feeding. Unfortunately, a low success rate (68%) and a high ad- surgery.
verse event rate (22.5%) have been documented in the largest Complications are quite common after surgical gastros-
series to date [43]. tomy. This may reflect the poor nutritional status and asso-
ciated medical problems in many patients who undergo this
procedure. Potential complications include wound infection,
dehiscence, gastrostomy disruption, internal or external leak-
Fluoroscopic Technique age, gastric hemorrhage, and tube migration.
Percutaneous gastrostomy and gastrojejunostomy can also be
performed using fluoroscopy [4446]. The stomach is insuf- NeedleCatheter Jejunostomy
flated with air using a nasogastric tube or a skinny needle if the
patient is obstructed proximally. Once the stomach is distended The needlecatheter jejunostomy procedure consists of the in-
and position is checked again with fluoroscopy, the stomach sertion of a small (5-Fr) polyethylene catheter into the small
is punctured with an 18-gauge needle. A heavy-duty wire is intestine at the time of laparotomy for another indication. Kits
passed and the tract is dilated to 7 Fr. A gastrostomy tube may containing the necessary equipment for the procedure are avail-
then be inserted into the stomach. An angiographic catheter is able from commercial suppliers. A needle is used to create
introduced and manipulated through the pylorus. The percu- a submucosal tunnel from the serosa to the mucosa on the
taneous tract is then further dilated and the gastrojejunostomy antimesenteric border of the jejunum. A catheter is inserted
tube is advanced as far as possible. through the needle and then the needle is removed. The catheter
is brought out through the anterior abdominal wall and the
limb of the jejunum is secured to the anterior abdominal wall
Complications with sutures. The tube can be used for feeding immediately af-
ter the operation. The potential complications are similar to
The most common complication after percutaneous placement those associated with gastrostomy, but patients may have a
of enteral feeding tubes is infection, usually involving the cu- higher incidence of diarrhea. Occlusion of the needlecatheter
taneous exit site and surrounding tissue [47]. Gastrointestinal jejunostomy is common because of its small luminal diameter,
hemorrhage has been reported, but it is usually due to excessive and elemental nutritional formulas are preferentially used.
tension on the tube, leading to necrosis of the stomach wall.
Gastrocolic fistulas, which develop if the colon is interposed
between the anterior abdominal wall and the stomach when Transgastric Jejunostomy
the needle is introduced, have been reported. Adequate tran-
sillumination aids in avoiding this complication. Separation of Critically ill patients who undergo laparotomy commonly re-
the stomach from the anterior abdominal wall can occur, re- quire gastric decompression and a surgically placed tube for
sulting in peritonitis when enteral feeding is initiated. In most enteral nutritional support. Routine placement of separate gas-
instances, this complication is caused by excessive tension on trostomy and jejunostomy tubes is common in this patient pop-
the gastrostomy tube. Another potential complication is pneu- ulation and achieves the objective of chronic gastric decompres-
moperitoneum, secondary to air escaping after puncture of the sion and early initiation of enteral nutritional support through
stomach during the procedure, and is usually clinically insignif- the jejunostomy. Technical advances in surgically placed enteral
icant. If the patient develops fever and abdominal tenderness, a feeding tubes led to the development of transgastric jejunos-
Gastrografin study should be obtained to exclude the presence tomy [49] and duodenostomy tubes, which allow simultane-
of a leak. ous decompression of the stomach and distal feeding into the
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140 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

problems with distention and diarrhea. Gastric residuals tend


to be smaller with continuous pump-fed infusions, and the risk
of aspiration may be decreased. In adult burn and trauma pa-
Anchors held down tients, continuous feedings are associated with less stool fre-
by sterile tape
quency and shorter time to achieve nutritional goals [50,51].

MEDICATIONS
When medications are administered via an enteric feeding tube,
Flange held
by anchors it is important to be certain that the drugs are compatible with
each other and with the enteral formula. In general, medica-
tions should be delivered separately rather than as a combined
bolus. For medications that are better absorbed in an empty
stomach, tube feedings should be suspended for 30 to 60 min-
utes before administration.
FIGURE 16.3. Transgastric duodenal feeding tube, which allows si- Medications should be administered in an elixir formulation
multaneous gastric decompression and duodenal feeding, can be placed via enteral feeding tubes whenever possible to prevent occlu-
percutaneously (with endoscopic or fluoroscopic assistance) or surgi- sion of the tube. Enteral tubes should always be flushed with
cally. 20 mL of saline after medications are administered. To use
an enteral feeding tube to administer medications dispensed in
tablet form, often the pills must be crushed and delivered as
duodenum or jejunum. The advantage of these tubes is that slurry mixed with water. This is inappropriate for some med-
only one enterotomy into the stomach is needed, eliminating ications, however, such as those absorbed sublingually or for-
the possible complications associated with open jejunostomy mulated as a sustained-released tablet or capsule.
tube placement. In addition, only one tube is necessary for
gastric decompression and jejunal feeding, eliminating the po-
tential complications of two separate tubes for this purpose. COMPLICATIONS
The transgastric jejunostomy tube is placed surgically in the
same manner as a gastrostomy tube, and the distal portion of Enteral tube placement is associated with few complications
the tube is advanced manually through the pylorus into the if practitioners adhere to appropriate protocols and pay close
duodenum, with its final tip resting as far distally as possible attention to the details of the procedures [52].
in the duodenum or jejunum (Fig. 16.3). The transgastric je-
junostomy tube is preferred to transgastric duodenostomy tube
because it is associated with less reflux of feedings into the Nasopulmonary Intubation
stomach and a decreased risk of aspiration pneumonia. Sur-
gical placement of transgastric jejunostomy tubes at the time Passage of an enteral feeding tube into the tracheobronchial
of laparotomy is recommended for patients who likely require tree most commonly occurs in patients with diminished cough
prolonged gastric decompression and enteral feeding. or gag reflexes due to obtundation, altered mental status, or
other causes such as the presence of endotracheal intubation.
The presence of a tracheostomy or endotracheal tube does not
DELIVERING THE TUBE-FEEDING guarantee proper placement. A chest (or upper abdominal)
FORMULA radiograph should always be obtained before initiating tube
feedings with a new tube to ensure that the tube is properly
The enteral formula can be delivered by intermittent bolus feed- positioned. Endotracheal or transpulmonary placement of a
ing, gravity infusion, or continuous pump infusion. In the in- feeding tube can be associated with pneumothorax, hydrotho-
termittent bolus method, the patient receives 300 to 400 mL of rax, pneumonia, pulmonary hemorrhage, abscess formation,
formula every 4 to 6 hours. The bolus is usually delivered with or death. A chest radiograph or a means of detecting CO2
the aid of a catheter-tipped, large-volume (60-mL) syringe. The through the tube after it has been inserted 30 cm should be
main advantage of bolus feeding is simplicity. This approach obtained to prevent inadvertent placement of small-bore feed-
is often used for patients requiring prolonged supplemental ing tubes into the lungs.
enteral nutritional support after discharge from the hospital.
Bolus feeding can be associated with serious side effects, how-
ever. Bolus enteral feeding into the stomach can cause gastric Aspiration
distention, nausea, cramping, and aspiration. The intermittent
bolus method should not be used when feeding into the duo- Pulmonary aspiration is a serious and potentially fatal com-
denum or jejunum because boluses of formula can cause dis- plication of enteral nutritional support [53]. The incidence
tention, cramping, and diarrhea. of this complication is variable and depends on the patient
Gravity-infusion systems allow the formula to drip contin- population studied. The two most common bedside tests for
uously during 16 to 24 hours or intermittently during 20 to detecting aspiration in tube-fed patients include adding dye
30 minutes, four to six times per day. This method requires to the formula and observing for its appearance in tracheo-
constant monitoring because the flow rate can be extremely ir- bronchial secretions, and using glucose oxidase reagent strips
regular. The main advantages of this approach are simplicity, to test tracheobronchial secretions for glucose-containing en-
low cost, and close simulation of a normal feeding pattern. teral formula [54]. No large prospective clinical trials have vali-
Continuous pump infusion is the preferred method for the dated the use and safety of bedside monitors for aspiration, and
delivery of enteral nutrition in the critically ill patient. A peri- their use should be abandoned. Nonrecumbent positioning is
staltic pump can be used to provide a continuous infusion of an evidence-based method for aspiration prevention that needs
formula at a precisely controlled flow rate, which decreases to be initiated in all patients receiving enteral nutrition.
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Chapter 16: Endoscopic Placement of Feeding Tubes 141

Major risk factors for aspiration include obtundation or


altered mental status, absence of cough or gag reflexes, delayed Bacterial Contamination
gastric emptying, gastroesophageal reflux, and feeding in the
supine position. The risk of pulmonary aspiration is minimized Bacterial contamination of enteral solutions [5759] occurs
when the enteral feeding tube is positioned in the jejunum past when commercial packages are opened and mixed with other
the ligament of Treitz. substances, and more commonly, it occurs with hospital-
formulated and powdered feeds that require preparation com-
pared to commercially prepared, ready-to-feed enteral formu-
las supplied in cans. The risk of contamination also depends on
Gastrointestinal Intolerance the duration of feeding. Contaminated formula may also play a
significant role in the etiology of diarrhea in patients receiving
Delayed gastric emptying is sometimes improved by adminis- enteral nutrition.
tering the prokinetic agents metoclopramide (10 to 20 mg IV)
or erythromycin (200 mg IV). Dumping syndrome (i.e., diar-
rhea, distention, and abdominal cramping) can limit the use of Occluded Feeding Tubes
enteral feeding. Dumping may be caused by delivering a hyper-
osmotic load into the small intestine. Precipitation of certain proteins when exposed to an acid pH
Diarrhea in critically ill patients should not be attributed to may be an important factor leading to the solidifying of for-
intolerance of enteral feeding until other causes are excluded. mulas. Most premixed intact protein formulas solidify when
Other possible etiologies for diarrhea include medications (e.g., acidified to a pH less than 5. To prevent occlusion of feeding
magnesium-containing antacids and quinidine), alterations in tubes, the tube should be flushed with saline before and after
gut microflora due to prolonged antibiotic therapy, antibiotic- checking residuals. Small-caliber nasoenteric feeding tubes
associated colitis, ischemic colitis, viral or bacterial enteric in- should be flushed with 20 mL of saline every 4 to 6 hours
fection, electrolyte abnormalities, and excessive delivery of bile to prevent tube occlusion, even when enteral feedings are ad-
salts into the colon. Diarrhea can also be a manifestation of in- ministered by continuous infusion.
testinal malabsorption because of enzyme deficiencies or villous Medications are a frequent cause of clogging. When admin-
atrophy [55]. istering medications enterally, liquid elixirs should be used, if
Even if diarrhea is caused by enteral feeding, it can be con- available, because even tiny particles of crushed tablets can oc-
trolled in nearly 50% of cases by instituting a continuous infu- clude the distal orifice of small-caliber feeding tubes. If tablets
sion of formula (if bolus feedings are used), slowing the rate of are used, it is important to crush them to a fine powder and sol-
infusion, changing the formula, adding fiber to the enteral for- ubilize them in liquid before administration. In addition, tubes
mula, or adding antidiarrheal agents (e.g., tincture of opium). should be flushed with saline before and after the administra-
tion of any medications.
Several maneuvers are useful for clearing a clogged feeding
Metabolic Complications tube. The tube can be irrigated with warm saline, a carbonated
liquid, cranberry juice, or a pancreatic enzyme solution (e.g.,
Prerenal azotemia and hypernatremia can develop in patients Viokase). Commonly, a mixture of lipase, amylase, and pro-
fed with hyperosmolar solutions. The administration of free tease (Pancrease) dissolved in sodium bicarbonate solution (for
water, either added to the formula or as separate boluses to re- enzyme activation) is instilled into the tube with a syringe and
place obligatory losses, can avert this situation. Deficiencies of the tube clamped for approximately 30 minutes to allow enzy-
essential fatty acids and fat-soluble vitamins can develop after matic degradation of precipitated enteral feedings. The tube is
prolonged support with enteral solutions that contain minimal then vigorously flushed with saline. The pancreatic enzyme so-
amounts of fat. Periodic enteral supplementation with linoleic lution was successful in restoring tube patency in 96% of cases
acid or IV supplementation with emulsified fat can prevent this where formula clotting was the likely cause of occlusion and use
[56]. The amount of linoleic acid necessary to prevent chemical of cola or water had failed [60,61]. Prevention of tube clogging
and clinical fatty acid deficiency has been estimated to be 2.5 with flushes and pancreatic enzyme are therefore the methods
to 20.0 g per day. of choice in maintenance of chronic enteral feeding tubes.

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Chapter 17: Cerebrospinal Fluid Aspiration 143

CHAPTER 17 CEREBROSPINAL FLUID


ASPIRATION
JOHN P. WEAVER

This chapter presents guidelines for safe cerebrospinal fluid spinal fluid glucose concentration lag blood levels by about
(CSF) aspiration for the emergency department or the inten- 2 hours. Increased CSF glucose is nonspecific and usually re-
sive care physician, and provides a basic understanding of the flects hyperglycemia. Hypoglycorrhachia can be the result of
indications, techniques, and potential complications of these any inflammatory or neoplastic meningeal disorder, and it re-
procedures. flects increased glucose use by nervous tissue or leukocytes and
Physicians and supervised physician extenders routinely inhibited transport mechanisms. Elevated lactate levels caused
and safely perform CSF aspiration procedures with necessary by anaerobic glycolysis in bacterial and fungal meningitis usu-
equipment and sterile supplies readily accessible in most acute ally accompany lower glucose concentrations.
hospital patient care units. Most CSF aspirations are performed CSF protein content is usually less than 0.5% of that in
using local anesthesia alone, without sedation. Because it may plasma with an intact bloodbrain barrier. Albumin consti-
be a painful and anxiety-provoking procedure, sedation may be tutes up to 75% of CSF protein, and immunoglobulin G (IgG)
required for an uncooperative patient or for the pediatric popu- is the major component of the -globulin fraction. IgG freely
lation [1,2]. Radiographic imaging (fluoroscopy or ultrasound) traverses a damaged bloodbrain barrier. Although often non-
is needed in situations in which external anatomic landmarks specific, elevated CSF protein is an indicator of CNS pathology.
provide inadequate guidance for safe needle placement or when There is a gradient of total protein content in the spinal CSF
needle placement using external landmarks alone has proved to column, with the highest level normally found in the lumbar
be unsuccessful due to anatomic variations caused by trauma, subarachnoid space at 20 to 50 mg per dL. This is followed by
operative scar, congenital defects, or degenerative changes. Flu- the cisterna magna at 15 to 25 mg per dL and the ventricles at
oroscopy may be used for complicated lumbar puncture, C12 6 to 12 mg per dL. A value exceeding 500 mg per dL is compat-
puncture, and myelography. Computed tomography (CT) or ible with an intraspinal tumor or spinal compression causing a
magnetic resonance imaging (MRI) may be used for stereotac- complete subarachnoid block, meningitis, or bloody CSF [3].
tic placement of ventricular catheters. Clinicians should recog- Low protein levels are seen in healthy children younger than
nize the need for specialized equipment and training in certain 2 years, pseudotumor cerebri, acute water intoxication, and
cases. leukemic patients.
A normal CSF cell count includes no erythrocytes and a
maximum of five leukocytes per milliliter. A greater number of
CEREBROSPINAL FLUID ACCESS white blood cells (WBCs) are normally found in children (up to
10 per milliliter, mostly lymphocytes). Pathologically, increased
WBCs are present in infection, leukemia, GuillianBarre
Diagnostic Objectives syndrome, hemorrhage, encephalitis, and multiple sclerosis
(MS).
CSF analysis continues to be a major diagnostic tool in many
diseases. The most common indication for CSF sampling is
the suspicion of a cerebral nervous system (CNS) infection.
Hemorrhage
CSF is also analyzed for the diagnosis of subarachnoid hem- A nontraumatic SAH in the adult population may be due to
orrhage (SAH), demyelinating diseases, CNS spread of neo- a ruptured aneurysm. A paroxysmal severe headache is the
plasm, and CNS degenerative conditions. CSF access is neces- classic symptom of aneurysm rupture, but atypical headaches
sary for neurodiagnostic procedures, such as myelography and reminiscent of migraine are not uncommon. Warning leaks or
cisternography, and studies for device patencies (tube studies) a sentinel headache occurring at least 4 weeks prior to the
that require injection of contrast agents. CSF access for pressure diagnosis of SAH was reported by Beck et al. [4] in 17.3% of
recording is also important in the diagnosis of normal-pressure patients with subsequent diagnosis of SAH.
hydrocephalus, benign intracranial hypertension, and head Leblanc [5] reported that up to 50% of patients with a
injury. warning leak headache are undiagnosed after evaluation by
CSF is an ultrafiltrate of plasma and is normally clear and their physician and 55% of patients with premonitory warning
colorless. Its analysis is a sample of the fluid surrounding the headaches had normal CT findings, but all had a positive find-
brain and spinal cord. Abnormalities of color and clarity can ing of SAH on lumbar puncture. Lumbar puncture is indicated
reflect the presence of cells, protein, hemosiderin, or bilirubin with such presenting headache if the head CT is normal and if
that indicates pathologic processes. The diagnostic tests per- the clinical history and presentation are typical for aneurysm
formed on the aspirated CSF depend on the patients age, his- rupture.
tory, and differential diagnosis. A basic profile includes glucose A lumbar puncture should not be performed without prior
and protein values, a blood cell count, Gram stain, and aerobic CT if the patient has any focal neurologic deficit. The neuro-
and anaerobic cultures. CSF glucose depends on blood glucose logic abnormality might indicate the presence of an intracranial
levels and is usually equivalent to two-thirds of the serum glu- mass lesion, and lumbar puncture can increase the likelihood of
cose. It is slightly higher in neonates. Glucose is transported downward transtentorial herniation. SAH can also cause acute
into the CSF via carrier-facilitated diffusion, and changes in obstructive hydrocephalus by intraventricular extension or
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144 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

obstruction to CSF resorptive mechanisms at the arach- Aspiration from the reservoir or valve system of a shunt can
noid granulations. The CT scan would demonstrate ventricu- be performed to determine patency and collect CSF to diag-
lomegaly, which is best treated by CSF access and diversion nose an infectious process. The necessity of and procedure for
using a ventricular catheter. a shunt tap is best left to a neurosurgeon. Shunt aspiration is an
A traumatic lumbar puncture presents a diagnostic invasive procedure that carries a risk of contaminating the sys-
dilemma, especially in the context of diagnosing suspected tem with skin flora, and the resultant shunt infection requires
SAH. Differentiating characteristics include a decreasing red a lengthy hospitalization for shunt externalization, antibiotic
blood cell count in tubes collected serially during the proce- treatment, and replacement of all hardware. Therefore, CSF
dure, the presence of a fibrinous clot in the sample, and a typ- collection by shunt tap should be performed very selectively
ical ratio of about 1 leukocyte per 700 red blood cells. Xan- and after other potential sources of infection have been evalu-
thochromia is more indicative of SAH and is quickly evaluated ated. When shunt failure is due to distal obstruction, aspiration
by spinning a fresh CSF sample and comparing the color of the of CSF may temper neurologic impairment and even be lifesav-
supernatant to that of water. In performing this test, the use of ing until surgical revision can be performed.
a spectrophotometer is much more sensitive than by visual in-
spection. Spinal fluid accelerates red blood cell hemolysis, and Normal-Pressure Hydrocephalus
hemoglobin products are released within 2 hours of the initial
hemorrhage, creating the xanthochromia. Associated findings, Serial lumbar punctures or continuous CSF drainage via a lum-
such as a slightly depressed glucose level, increased protein, bar subarachnoid catheter can be used as provocative diagnos-
and an elevated opening pressure, are also more suggestive of tic tests to select patients who would benefit from a shunt for
the presence of an SAH. CSF diversion. The results have a positive predictive value if
the patients gait improves. Lumbar CSF access may also be
used for infusion tests, measurement of CSF production rate,
Infection pressurevolume index, and outflow resistance or absorption.
CSF evaluation is the single most important aspect of the labo- Some studies suggest that these values are also predictive of
ratory diagnosis of meningitis. The analysis usually includes a therapeutic CSF diversion [810].
Gram stain, blood cell count with white cell differential, pro-
tein and glucose levels, and aerobic and anaerobic cultures with Benign Intracranial Hypertension
antibiotic sensitivities. With suspicion of tuberculosis or fun- (Pseudotumor Cerebri)
gal meningitis, the fluid is analyzed by acid-fast stain, India Benign intracranial hypertension occurs in young persons, of-
ink preparation, cryptococcal antigen, and culture in appro- ten obese young women. Intracranial pressure (ICP) is elevated
priate media. More extensive cultures may be performed in the without focal deficits and in the absence of ventriculomegaly
immunocompromised patient. or intracranial mass lesions [11]. The condition causes blind-
Immunoprecipitation tests to identify bacterial anti- ness, and most patients demonstrate some visual loss. Etiologic
gens for Streptococcus pneumoniae, streptococcus group B, factors for childhood presentation include chronic middle ear
Haemophilus influenzae, and Neisseria meningitidis (meningo- infection, dural sinus thrombosis, head injury, vitamin A over-
coccus) allow rapid diagnosis and early specific treatment. dosage, tetracycline exposure, internal jugular venous throm-
Polymerase chain reaction testing can be performed on CSF for bosis, and idiopathic causes. Some authors have proposed a
rapid identification of several viruses, particularly those com- broader definition of the pseudotumor cerebri syndrome on
monly responsible for CNS infections in patients with acquired the basis of the underlying pathophysiologic mechanism of the
immunodeficiency syndrome. Polymerase chain reaction test- presumed CSF circulation disorder [12].
ing exists for herpes, varicella zoster, cytomegalovirus, and Lumbar puncture demonstrates an elevated ICP (up to
EpsteinBarr virus, as well as toxoplasmosis and Mycobac- 40 cm H2 O), and CSF dynamics demonstrates an increase
terium tuberculosis [6]. If the clinical suspicion is high for in outflow resistance. Serial daily punctures can be therapeu-
meningitis, administration of broad-spectrum antibiotic ther- tic, with CSF aspirated until closing pressure is within nor-
apy should be initiated without delay following CSF collection mal limits (<20 cm H2 O). In some cases, this can restore the
[7]. balance between CSF formation and absorption; other cases
require medical therapy, such as weight loss, steroids, acetazo-
Shunt Malfunction lamide, diuretics, and glycerol. If all these therapeutic interven-
tions fail, placement of a permanent shunting system may be
A ventriculoperitoneal shunt is the most commonly encoun- necessary.
tered implanted system for CSF diversion. The system consists
of a ventricular catheter connected to a reservoir and valve
mechanism at the skull and a catheter that passes in the sub-
Neoplasms
cutaneous soft tissue in the neck and anterior chest wall to The subarachnoid space can be infiltrated by various primary
the peritoneum. The distal tubing can be alternatively inserted or secondary tumors, giving rise to symptoms of meningeal
in the jugular vein, the pleura, or even the urinary bladder. irritation. CSF cytology can determine the presence of neo-
Proximal shunt failure of the ventricular catheter may occur plastic cells, although their complete identification is not al-
due to choroid plexus obstruction or cellular debris from CSF ways possible. Systemic neoplasms, such as melanoma or breast
infection. Valve or distal tubing obstruction occurs also from cancer, have a greater propensity to metastasize into the CSF
cellular debris, from disconnection, poor CSF absorption, or spaces than do primary CNS tumors and may even present
formation of an intra-abdominal pseudocyst. primarily as meningeal carcinomatosis. Ependymoma, medul-
The clinical presentation of an obstructed shunt is variable. loblastoma or primitive neuroectodermal tumor, germinoma,
It may be slowly progressive and intermittent, or there may be a and high-grade glioma are the most commonly disseminated
rapid decline in mentation progressing into a coma. A CT scan primary tumors. Hematopoietic cancers such as leukemia and
should be performed immediately to determine ventricular size. lymphoma also frequently infiltrate the subarachnoid spaces
Ventriculomegaly is a reliable indicator of a malfunctioning with little or no parenchymal involvement. CSF sampling is
shunt; however, the CT scan should be compared with previous useful for an initial diagnostic and screening tool in the neuro-
studies because the ventricular system in a shunted patient is logically intact patient who harbors a tumor type with high risk
often congenitally or chronically abnormal. of CNS relapse. Lymphoma cells in primary CNS lymphoma
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Chapter 17: Cerebrospinal Fluid Aspiration 145

are present in increased number and pleocytosis correlates with positive for glucose. A chloride level often shows a higher value
positive cytology [13]. A generous amount of CSF or multiple than in peripheral blood, but identification of 2 -transferrin is
samples may be required for diagnosis and cisternal puncture the most accurate diagnostic for CSF. This protein is produced
may enhance the diagnosis if the lumbar CSF is nondiagnos- by neuraminidase in the brain and is uniquely found in the
tic. Acute leukemias that tend to invade the CNS include acute spinal and perilymph fluids [19].
lymphocytic leukemia, acute nonlymphocytic leukemia, acute Elevation of the patients head is the primary treatment of
myelogenous leukemia, acute myelomonocytic leukemia, and CSF leak. Placement of a lumbar drainage catheter or daily lum-
acute undifferentiated leukemia [14]. bar punctures should be used if conservative therapy fails. The
use of a continuous lumbar drainage by a catheter is somewhat
Myelography controversial because of the potential for intracranial contam-
ination from the sinuses if the ICP is lowered. To help prevent
Lumbar puncture is the most common means of access for lum- such complications, the lumbar drain collection bag can be
bar and cervical myelography because the density of contrast maintained no lower than the patients shoulder level and the
material is higher than CSF and may be directed by gravity to duration of drainage should not exceed 5 days.
the area of interest. Cervical C12 puncture had been a usual
access route for cervical myelography, but now, it is often re-
served for patients in whom a successful lumbar puncture is not Intracranial Hypertension
possible due to extensive arachnoiditis, epidural tumor, severe
Intracranial hypertension can cause significant neurologic mor-
spinal stenosis, or CSF block.
bidity or even death. Access to the intracranial CSF space is
useful for diagnosis and treatment [20]. A ventriculostomy is
Other Neurologic Disorders commonly used both as an ICP monitor and as a means to treat
There is extensive literature on CSF changes in demyelinat- intracranial hypertension by CSF drainage. An ICP-measuring
ing diseases, including MS. Typical lumbar puncture findings device should be placed following traumatic brain injury for
are normal ICP, normal glucose levels, mononuclear pleocy- patients who exhibit a Glasgow Coma Scale score less than
tosis, and elevated protein levels due to increased endothelial 8, a motor score less than 6 (not aphasic), and with initial
permeability. Immunoelectrophoresis reveals elevated IgG and CT findings of diffuse brain edema, intercranial hematoma,
oligoclonal bands that suggest inflammation in the CNS and cortical contusions, or absent or compressed basal cisterns
may be a sign of MS [15,16]. [21]. ICP monitoring can also be indicated in cerebrovascu-
CSF findings described in other disease states include ele- lar diseases, including aneurysmal SAH, spontaneous cerebral
vated tau protein and decreased -amyloid precursor protein hematoma, ischemic and hypoxic cerebral insults, and intra-
in Alzheimers disease and the presence of anti-GM1 antibod- ventricular hemorrhage. Obstructive hydrocephalus is another
ies and cytoalbumin dissociation in GuillainBarre syndrome major indication for placement of a ventricular catheter for
[17]. drainage and monitoring. ICP may be elevated due to cerebral
edema that surrounds tumors, intracranial hematomas, stroke,
and traumatic contusions, or that occurs postoperatively or
Therapeutic Intervention following cranial radiation therapy. Diffuse brain swelling also
occurs in the setting of inflammatory and infectious disor-
ders such as Reyes syndrome or meningitis, or as a result
Fistulas
of hyperthermia, carbon dioxide retention, or intravascular
CSF leaks occur due to a variety of nontraumatic and traumatic congestion.
etiologies. Orthostatic headaches are a characteristic symptom
of CSF leak, and rhinorrhea may be evident. Iatrogenic post-
operative CSF leaks may occur following surgery at the skull Drug Therapy
base as a result of dural or bony defects. CSF fistulas following The CSF can be a route of administration for medications
middle cranial fossa or cerebellopontine angle surgery occur in- such as chemotherapeutic agents and antibiotics. Treatment
frequently, and CSF usually leaks through the auditory tube to of lymphoma and leukemia often involves intrathecal injec-
the nasopharynx. Dural closure in the posterior fossa following tions of various agents, which may be infused through a lum-
suboccipital craniectomy is often difficult and not watertight. bar route or an intraventricular injection via an implanted
A fistula in that area usually results in a pseudomeningocele, reservoir. Meningeal carcinomatosis is treated by intrathecal
which is clinically apparent as subcutaneous swelling at the in- chemotherapy (e.g., methotrexate). Serial injections of small
cision site. Leaks following lumbar surgery are unusual, but amounts are performed in an attempt to minimize neurotoxic-
they may occur as a result of recent myelography, dural tear, ity, and the use of a ventricular reservoir may be less traumatic
or inadequate dural closure [18]. In pediatric patients, repair for the patient than that of multiple lumbar punctures. Treat-
of meningoceles or other spina bifida defects are more likely to ment of meningitis and ventriculitis may include intrathecal
present with a CSF leak because of dural or fascial defects. antibiotics in addition to systemic therapy. Careful dosage and
The most common presentation of a CSF fistula follows administration are recommended, especially if the ventricular
trauma. Basilar skull fractures that traverse the ethmoid or route is used, as many antibiotics can cause seizures or an in-
frontal sinuses can cause CSF rhinorrhea. Fractures along the flammatory ventriculitis when given intrathecally.
long axis of the petrous bone usually involve the middle ear,
causing the hemotympanum noted on examination and CSF ot-
orrhea if the tympanic membrane is ruptured. Most CSF leaks
present within 48 hours, but delayed leaks are not uncommon
because the fistula can be occluded with adhesions, hematoma, TECHNIQUES OF CEREBROSPINAL
or herniated brain tissue, which temporarily tamponades the FLUID ACCESS
defect.
The diagnosis of a leak may be easily made on clinical exam- There are several techniques for CSF aspiration. All procedures
ination; however, at times, the nature of a drainage fluid is should be performed using sterile technique (including sterile
uncertain and laboratory characterization is necessary. Dipping gloves and a mask), and the skin is prepared with antiseptic
the fluid for glucose is misleading because nasal secretions are solution and draped with sterile towels.
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146 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

Lumbar Puncture
Lumbar puncture is a common procedure that is readily per-
formed by the general practitioner at the bedside and can be
performed in any hospital or outpatient setting where commer-
cially prepared lumbar puncture trays are available. In patients
with advanced spinal degeneration, extensive previous lumbar
surgery for congenital defects and the assistance of a radiol-
ogist for needle placement using fluoroscopy or ultrasonog-
raphy may be required. Contraindications to lumbar punc-
ture include skin infection at the entry site, anticoagulation or
blood dyscrasias, papilledema in the presence of supratentorial
masses, posterior fossa lesions, and known spinal subarachnoid
block or spinal cord arteriovenous malformations.
In adults, CSF aspirations are adequately performed under
local anesthesia using 1% lidocaine without premedication. In
the pediatric population, however, sedation is often required
and allows for a smoother procedure. This is also true in the
case of anxious, confused, or combative adult patients.
Oral or rectal chloral hydrate may be used in small children,
and moderate sedation using intravenous midazolam and fen-
tanyl or dexmedetomidine can be highly successful in appropri- FIGURE 17.2. Patient sitting on the edge of the bed leaning on bedside
ately monitored adults and children when performed in a mon- stand. [From Davidson RI: Lumbar puncture, in VanderSalm TJ (ed):
itored setting by an experienced individual. The application of Atlas of Bedside Procedures. 2nd ed. Boston, Little, Brown, 1988, with
permission.]
a topical anesthetic, such as EMLA cream (2.5% lidocaine and
2.5% prilocaine), preceding injection can also be useful. Con-
versely, it has been demonstrated in a controlled clinical trial
that in the neonatal population, injection of a local anesthetic medullaris, which lies more caudal than in adults. The needle
for lumbar puncture is probably not required and does not is advanced with the stylet or obturator in place to maintain
reduce perceived stress or discomfort [22]. needle patency and prevent iatrogenic intraspinal epidermoid
Figures 17.1 and 17.2 depict some of the steps for lumbar tumors. The bevel of the needle should be parallel to the longi-
puncture. The patient is placed in the lateral knee-chest posi- tudinal fibers of the dura and spinal column. The needle should
tion or with the patient sitting leaning forward over a bedside be oriented rostrally at an angle of about 30 degrees to the
table. The sitting position may be preferred for obese patients skin and virtually aimed toward the umbilicus. When properly
in whom adipose tissue can obscure the midline or in elderly pa- oriented, the needle passes through the following structures
tients with significant lumbar degenerative disease. Following a before entering the subarachnoid space: skin, superficial fas-
time-out (correct patient, procedure, site, and equipment), the cia, supraspinous ligament, interspinous ligament, ligamentum
local anesthetic is injected subcutaneously using a 25- or 27- flavum, epidural space with its fatty areolar tissue and internal
gauge needle. A 1.5-in. needle is then inserted through the skin vertebral plexus, dura, and arachnoid membrane (Fig. 17.3).
wheal and additional local anesthetic is injected along the mid- The total depth varies from less than 1 in. in the very young
line, thus anesthetizing the interspinous ligaments and muscles. patient to as deep as 4 in. in the obese adult. The kinesthetic
This small anesthetic volume is usually adequate; however, a sensations of passing through the ligaments into the epidural
more extensive field block is accomplished by additional injec-
tions on each side of the interspinous space near the lamina
[23].
The point of skin entry is midline at the level of the superior
iliac crests, which is usually between the spinous processes of
L3 to L4. Lower needle placement at L4 to L5 or L5 to S1 is
required in children and neonates to avoid injury to the conus

FIGURE 17.3. The spinal needle is advanced to the spinal subarach-


FIGURE 17.1. Patient in the lateral decubitus position with back on noid space and cerebrospinal fluid samples collected after opening
the edge of the bed and knees, hips, back, and neck flexed. [From pressure is measured. [From Davidson RI: Lumbar puncture, in Van-
Davidson RI: Lumbar puncture, in VanderSalm TJ (ed): Atlas of Bed- derSalm TJ (ed): Atlas of Bedside Procedures. 2nd ed. Boston, Little,
side Procedures. 2nd ed. Boston, Little, Brown, 1988, with permission.] Brown, 1988, with permission.]
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Chapter 17: Cerebrospinal Fluid Aspiration 147

space followed by dural puncture are quite consistent and rec- An uncommon sequela of lumbar puncture or continuous
ognized with practice. Once intradural, the bevel of the needle CSF drainage is hearing loss. Drainage decreases ICP, which is
is redirected in a cephalad direction in order to improve CSF transmitted to the perilymph via the cochlear aqueduct and can
flow. A spinal needle no smaller than 22 gauge should be used cause hearing impairment [35]. The rate of occurrence of this
for pressure measurement. The opening pressure is best mea- complication is reported to be 0.4%, but is probably higher
sured with the patients legs relaxed and extended partly from because it goes unrecognized and seems reversible. There are a
the knee-chest position. Pressure measurements may be difficult few documented cases of irreversible hearing loss [36].
in children and may be estimated using CSF flow rate [24]. Transient sixth-nerve palsy has also been reported, proba-
Once CSF is collected, the closing pressure is measured prior bly due to nerve traction following significant CSF removal.
to needle withdrawal. It is best to replace the stylet in the needle Neurovascular injury can occur uncommonly in the setting of
prior to exiting the subarachnoid space. CSF pressure measure- a subarachnoid block due to spinal tumors. In this situation,
ments are not accurate if performed in the sitting position due CSF drainage leads to significant traction and spinal coning
to the hydrostatic pressure of the CSF column above the entry with subsequent neurologic impairment [37,38].
point or if a significant amount of CSF was lost when the stylet
is first withdrawn. If necessary, the pressure could be measured
by reclining the patient to the lateral position once entry in the Lateral Cervical (C12) Puncture
CSF space has been secured.
Although a lumbar puncture is typically safe, there are a The C12 or lateral cervical puncture was originally developed
number of potential complications and risks involved. Hemor- for percutaneous cordotomy. It may be used for myelography
rhage is uncommon but can be seen in association with bleeding or aspiration of CSF if the lumbar route is inaccessible. It is
disorders and anticoagulation therapy. Spinal SAH has been most safely performed with fluoroscopic guidance with the pa-
reported in such conditions, resulting in blockage of CSF out- tient supine, the head and neck flexed, and the lateral neck
flow with subsequent back and radicular pain, sphincter distur- draped. The skin entry point is 1 cm caudal and 1 cm dorsal
bances, and even paraparesis [25]. Spinal subdural hematoma to the tip of the mastoid process. The site is infiltrated with
is likewise very infrequent, but it is associated with significant a local anesthetic, and the spinal needle is introduced and di-
morbidity that may require prompt surgical intervention. In- rected toward the junction of the middle and posterior thirds
fection by introduction of the patients skin flora or the opera- of the bony canal to avoid an anomalous vertebral or poste-
tors mouth or nose flora into the subarachnoid spaces, causing rior inferior cerebellar artery that may lie in the anterior half
meningitis, is uncommon and preventable if aseptic techniques of the canal. The stylet should be removed frequently to check
(including mask) are used. Risks of infection are increased in for CSF egress. When the procedure is performed under fluo-
serial taps or placement of lumbar catheters for the treatment roscopy, the needle is seen to be perpendicular to the neck and
of CSF fistulas. just under the posterior ring of C1. The same sensation is rec-
Postural headache is the most common complication fol- ognized when piercing the dura as in a lumbar puncture and
lowing lumbar puncture. Its reported frequency varies from the bevel is then directed cephalad in a similar fashion. Com-
1% to 70% [26]. It is thought to be due to excessive leakage of plications of the lateral cervical puncture include injury to the
CSF into the paraspinous spaces, resulting in intracranial hy- spinal cord or the vertebral artery and irritation of a nerve root,
potension with stretching and expansion of the pain-sensitive causing local pain and headache.
intracerebral veins. MRI has demonstrated a reduced CSF vol-
ume following lumbar puncture, but with no significant brain
displacement and no correlation with headache [27]. Psycho-
logic factors and previous history of headaches seem to strongly Cisternal Puncture
influence the patients risk of and tolerance to headache [28].
A smaller needle size, parallel orientation to the dural fibers, A cisternal puncture provides CSF access via the cisterna magna
a paramedian approach, and stylet reinsertion prior to with- when other routes are not possible. A preoperative lateral skull
drawal of the spinal needle have also been reported to decrease radiograph is performed to ensure normal anatomy. The pa-
the risk of headache after lumbar puncture [29]. tient is positioned sitting with the head slightly flexed. The
The choice of needle type has been the subject of litera- hair is removed in the occipital region and the area prepared,
ture debate. Several needle tip designs are available, includ- draped, and infiltrated with lidocaine. The entry point is in the
ing the traditional Quincke needle with a beveled cutting tip, midline between the external occipital protuberance in the up-
the Sprotte needle with a pencil point and side hole, and the per margin of the spinous process of C2 or via an imaginary
Whitacre needle, which is similar to the Sprotte needle but with line through both external auditory meati. The spinal needle is
a smaller side hole. The use of an atraumatic needle seems to be directed through a slightly cephalad course and usually strikes
adequate for the performance of a diagnostic lumbar puncture the occipital bone. It is then redirected more caudally in a step-
and is probably associated with a lower risk of a postpuncture wise fashion until it passes through the atlanto-occipital mem-
headache [30,31]. brane and dura, producing a popping sensation. The cisterna
Postdural puncture headache typically develops within 72 magna usually lies 4 to 6 cm deep to the skin; the needle should
hours and lasts 3 to 5 days. Conservative treatment con- not be introduced beyond 7.0 to 7.5 cm from the skin to prevent
sists of bed rest, hydration, and analgesics. Non-phenothiazine injury to the medulla or the vertebral arteries. The procedure
antiemetics are administered if the headache is associated with can be performed relatively safely in a cooperative patient as
nausea. If the symptoms are more severe, methylxanthines (caf- the cisterna magna is a large CSF space; however, it is rarely
feine or theophylline) are prescribed orally or parenterally. practiced due to the greater potential morbidity.
These agents are successful in up to 85% of patients [32]. Sev-
eral other pharmacologic agents are discussed in the literature,
but none seems to be as effective as caffeine. If the headache Aspiration of Reservoirs and Shunts
persists or is unaffected, an epidural blood patch is then recom-
mended because it is one of the most effective treatments for An implanted reservoir or shunt system should not be accessed
this condition [33]. Epidural injection of other agents, such as without prior consultation with a neurosurgeon, despite the
saline, dextran, or adenocorticotropic hormone, has also been apparent simplicity of the procedure itself. Violating implanted
described and may be valuable under certain conditions (e.g., systems carries several risks, including infection, which can re-
sepsis or acquired immunodeficiency syndrome) [34]. sult in a lengthy hospitalization, prolonged antibiotic course,
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148 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

ered. The needle is inserted perpendicular to the skin and into


the reservoir, to a total depth of 3 to 5 mm. A manometer is
then connected to the needle or butterfly tubing for pressure
measurement. CSF collection is performed and drug injection
is performed only if CSF flow is demonstrated. A dry tap
usually indicates faulty placement or catheter obstruction. Oc-
casionally, an old reservoir may have retracted into the burr
hole and not be palpable or may be too calcified for needle
penetration and some older shunting systems may not even
have a reservoir. Risks and complications of shunt aspiration
include improper insertion, contamination with skin flora, in-
troduction of blood in the shunt system, and choroid plexus
hemorrhage due to vigorous aspiration.

Lumboperitoneal Shunt
Lumboperitoneal shunts are placed via percutaneous insertion
of a lumbar subarachnoid catheter or through a small skin in-
FIGURE 17.4. Close-up view of ventricular reservoir in the calvarial cision. They are tunneled subcutaneously around the patients
burr hole, the funneled base connected directly to the proximal end of flank to the abdomen, where the distal catheter enters the peri-
the ventricular catheter. The distal perforated end is shown. toneal cavity through a separate abdominal incision. A reser-
voir or valve or both may be used and are located on the lateral
aspect of the flank. Careful palpation between the two inci-
and several operative procedures for shunt externalization, sions usually reveals the tubing path and reservoir placement
hardware removal, and insertion of a new shunt system. in the nonobese patient. The patient is placed in lateral decubi-
Subcutaneous reservoirs in ventriculoatrial or ventricu- tus position and a pillow under the dependent flank may be of
loperitoneal shunting systems are located proximal to the uni- assistance. The same technique as described for a ventricular
directional valve and can be accessed percutaneously. The reser- shunt is then performed. Fluid aspiration should be particu-
voirs are usually button-sized, measuring approximately 7 to larly gentle as an additional risk of this procedure is nerve root
10 mm in diameter and 2 mm in height. They can be located irritation.
in the burr hole directly connected to the ventricular catheter
(Fig. 17.4) or as an integral part of the valve system (Fig. 17.5). Ventricular Reservoirs
Indications for reservoir taps have been previously discussed.
The procedure can be performed in any hospital or out- Ventricular reservoirs are inserted as part of a blind system
patient setting. Gloves, mask, antiseptic solution, razor, sterile consisting of a catheter located in a CSF space, usually the
drapes, 23- or 25-gauge needle (short hub or butterfly), tu- lateral ventricle, and without distal runoff. Such systems are
berculin syringe, and sterile collection tubes are readied. The placed for CSF access purposes only, such as for instilla-
patient can be in any comfortable position that allows access tion of antibiotics or chemotherapeutic agents, or CSF aspi-
to the reservoir. Sedation may be required for toddlers, but is ration for treatment and monitoring. Ommaya reservoirs are
otherwise unnecessary. Reference to a skull radiograph may dome-shaped structures (Fig. 17.6) with a diameter of 1 to
be helpful in localization. The reservoir is palpated, overlying 2 cm and have a connecting port placed at their base or side.
hair is removed preferably with a clipper rather than a razor They are placed subcutaneously and attached to a ventricular
and the skin cleansed. Local anesthesia is usually not required
and the use of topical anesthetic creams is occasionally consid-

FIGURE 17.5. A domed reservoir in series in one type of shunt valve. FIGURE 17.6. Close-up view of a ventricular (Ommaya) double-
The large, clear-domed area for puncture lies immediately proximal to domed reservoir, the caudal half of which is designed to lie within
the one-way valve. the burr hole.
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Chapter 17: Cerebrospinal Fluid Aspiration 149

performed through the nondominant hemisphere and into the


frontal horn of the lateral ventricle. An alternate approach is
to cannulate the occipital horn or trigone through an occipital
entry point located 6 cm superior to the inion and 4 cm from
the midline. Premedication is not necessary unless the patient is
very anxious or combative. Radiographic guidance is typically
not required unless the procedure is being performed stereo-
tactically. CT or MRI stereotaxy is needed if the ventricles are
very small, as in diffuse brain swelling or slit ventricle syn-
drome. Complications of ventriculostomy placement include
meningitis or ventriculitis, scalp wound infection, intracranial
hematoma or cortical injury, and failure to cannulate the ven-
tricle.

Lumbar Drainage
Continuous CSF drainage via a lumbar catheter is useful in the
treatment of CSF fistulas and as a provocative test to demon-
strate the potential effects of shunting in normal-pressure
hydrocephalus or ventriculomegaly of various etiologies.
Commercially available lumbar drainage kits are closed sterile
FIGURE 17.7. Coronal section through the brain at the level of the
frontal horns, illustrating the subgaleal/epicalvarial location at the
systems that drain into a replaceable collection bag. Catheter
reservoir, with the distal perforated part of the catheter lying within placement is performed just as in lumbar puncture; however,
the ventricle. a large-bore Tuohy needle is used, through which the catheter
is threaded once CSF return has been confirmed. Needle ori-
entation follows the same guidelines as discussed for a lum-
subarachnoid catheter (Fig. 17.7). Aspiration technique is es- bar puncture and is even more important in the case of this
sentially the same as from a shunt reservoir; however, the Om- large-gauge needle. Epidural catheter kits could also be used,
maya reservoir is often larger and differs in shape from many although the catheters tend to be slightly stiffer and have a
shunt reservoirs. It is accessed, preferably, with a 25-gauge nee- narrower diameter. Complications include hemorrhage in the
dle or butterfly. CSF is allowed to flow by gravity if possible; epidural or subarachnoid space, infection, inability to aspirate
a volume equal to that to be instilled is removed and held CSF, CSF leak, nerve root irritation, and, most ominously, a
for analysis or reinjection. The antibiotic or chemotherapeu- supratentorial subdural hematoma secondary to overdrainage.
tic agent is injected; 1 mL of CSF or sterile saline can be used This complication tends to be more common in elderly indi-
to flush the dose into the ventricle, or gentle barbotage of the viduals. The potential for overdrainage is significant because
reservoir may be performed to achieve the same goal. Risks of the large diameter of the catheter and because the amount
and complications are essentially the same as in shunt aspira- of drainage depends on the cooperation of the patient and the
tions (i.e., infection, bleeding, and improper insertion), with nursing staff.
the addition of chemical ventriculitis or arachnoiditis.

SUMMARY
Ventriculostomy
Of the various techniques available for CSF access, lumbar
A ventriculostomy is a catheter placed in the lateral ventricle for puncture is the procedure most commonly and safely per-
CSF drainage or ICP monitoring and treatment. It is performed formed by the general practitioner. Other techniques are de-
by a neurosurgeon in the operating room or at the bedside in scribed that may require the assistance of a radiologist, neurol-
the intensive care unit or emergency department. It is usually ogist, anesthesiologist, or neurosurgeon.

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Surgeons, Joint Section on Neurotrauma and Critical Care: guidelines for the 32. Ahmed SV, Jayawarna C, Jude E: Post lumbar puncture headache: diagnosis
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24:S1, 2007. 33. van Kooten F, Oedit R, Bakker S, et al: Epidural blood patch in post dural
22. Porter FL, Miller JP, Cole FS, et al: A controlled clinical trial of local anes- puncture headache: a randomized, observer-blind, controlled clinical trial.
thesia for lumbar punctures in newborns [see comments]. Pediatrics 88:663, J Neurol Neurosurg Psychiatry 79:553, 2007.
1991. 34. Choi A, Laurito CE, Cunningham FE: Pharmacologic management of post-
23. Wilkinson HA: Technical note: anesthesia for lumbar puncture. JAMA dural headache. Ann Pharmacother 30:831, 1996.
249:2177, 1983. 35. Walsted A, Salomon G, Thomsen J: Hearing decrease after loss of
24. Ellis RW III, Strauss LC, Wiley JM, et al: A simple method of estimating cere- cerebrospinal fluid: a new hydrops model? Acta Otolaryngol 111:468,
brospinal fluid pressure during lumbar puncture. Pediatrics 89:895, 1992. 1991.
25. Scott EW, Cazenave CR, Virapongse C: Spinal subarachnoid hematoma 36. Michel O, Brusis T: Hearing loss as a sequel of lumbar puncture. Ann Otol
complicating lumbar puncture: diagnosis and management. Neurosurgery Rhinol Laryngol 101:390, 1992.
25:287, 1989. 37. Wong MC, Krol G, Rosenblum MK: Occult epidural chloroma compli-
26. Strupp M, Brandt T: Should one reinsert the stylet during lumbar puncture? cated by acute paraplegia following lumbar puncture. Ann Neurol 31:110,
N Engl J Med 336:1190, 1997. 1992.
27. Grant F, Condon B, Hart I, et al: Changes in intracranial CSF volume af- 38. Mutoh S, Aikou I, Ueda S: Spinal coning after lumbar puncture in prostate
ter lumbar puncture and their relationship to post-LP headache. J Neurol cancer with asymptomatic vertebral metastasis: a case report. J Urol 145:834,
Neurosurg Psychiatry 54:440, 1991. 1991.

CHAPTER 18 PERCUTANEOUS
SUPRAPUBIC CYSTOSTOMY
SATYA ALLAPARTHI, K.C. BALAJI AND PHILIP J. AYVAZIAN

Percutaneous suprapubic cystostomy was described four cen- may require a larger bore catheter, such as 20 or 22 French (Fr).
turies ago; safety of the procedure was first demonstrated by When dealing with urethral strictures, a smaller bore catheter
Garson and Peterson in 1888. The first modern method was should be used, such as 12 or 14 Fr. Patients with a history of
the Campbell trocar set, described in 1951 [1]. It is used to prior prostatic surgery such as transurethral resection of the
divert urine from the bladder when standard urethral catheter- prostate, open prostatectomy, or radical prostatectomy may
ization is impossible or undesirable [2]. In emergency situ- have an irregular bladder neck as a result of contracture after
ations, the majority of these patients are men with urethral surgery. The use of a coude-tip catheter, which has an upper
stricture or complex prostatic disease or patients with trauma deflected tip, may help in negotiating the altered anatomy af-
with urethral disruption. Complete urethral transection asso- ter prostate surgery. The presence of a high-riding prostate or
ciated with a pelvic fracture is an absolute indication for emer- blood at the urethral meatus suggests urethral trauma. In this
gent suprapubic cystostomy. The procedure for placement of a situation, urethral integrity must be demonstrated by retro-
small-diameter catheter is rapid, safe, and easily accomplished grade urethrogram before urethral catheterization is attempted.
at the bedside under local anesthesia. This chapter first ad- Urethral catheterization for gross hematuria requires large
dresses methods for urethral catheterization before discussing catheters, such as 22 or 24 Fr, which have larger holes for
the percutaneous approach. irrigation and removal of clots. Alternatively, a three-way ure-
thral catheter may be used to provide continuous bladder ir-
rigation to prevent clotting. Large catheters impede excretion
of urethral secretions, however, and can lead to urethritis or
URETHRAL CATHETERIZATION epididymitis if used for prolonged periods.
Urethral catheterization remains the principal method for blad-
der drainage. The indications for the catheter should be clari-
fied because they influence the type and size of catheter to be Technique
used [3]. A history and physical examination with particular
attention to the patients genitourinary system are important. In male patients, after the patient is prepared and draped,
Catheterization may be difficult with male patients in several 10 mL of a 2% lidocaine hydrochloride jelly is injected ret-
instances. Patients with lower urinary tract symptoms (e.g., uri- rograde into the urethra. Anesthesia of the urethral mucosa
nary urgency, frequency, nocturia, decreased stream, and hesi- requires 5 to 10 minutes after occluding the urethral meatus
tancy) may have benign prostatic hypertrophy. These patients either with a penile clamp or manually to prevent loss of the
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 18: Percutaneous Suprapubic Cystostomy 151

jelly [4]. The balloon of the catheter is tested, and the catheter TA B L E 1 8 . 2
tip is covered with a water-soluble lubricant. After stretching
the penis upward and perpendicular to the body, the catheter RELATIVE CONTRAINDICATIONS TO
is inserted into the urethral meatus. The catheter is advanced PERCUTANEOUS SUPRAPUBIC CYSTOTOMY
up to the hub to ensure its entrance into the bladder. To pre-
vent urethral trauma, the balloon is not inflated until urine is Nonpalpable bladder
observed draining from the catheter. Irrigation of the catheter Previous lower abdominal surgery
with normal saline helps verify the position. A common site of Coagulopathy
resistance to catheter passage is the external urinary sphincter Known bladder tumor
within the membranous urethra, which may contract voluntar- Clot retention
ily. Any other resistance may represent a stricture, necessitating
urologic consultation. In patients with prior prostate surgery,
an assistants finger placed in the rectum may elevate the ure-
thra and allow the catheter to pass into the bladder. with saline to distend it. In men, a 14-Fr catheter is placed in the
In female patients, short, straight catheters are preferred. fossa navicularis just inside the urethral meatus and the balloon
Typically, a smaller amount of local anesthesia is used. Dif- is filled with 2 to 3 mL of sterile water to occlude the urethra.
ficulties in catheter placement occur after urethral surgery or Saline is injected slowly into the catheter until the bladder is
vulvectomy, or with vaginal atrophy or morbid obesity. In these palpable and then the suprapubic tube may be placed. In pa-
cases, the meatus is not visible and may be retracted under the tients with a contracted neurogenic bladder, it is impossible to
symphysis pubis. Blind catheter placement over a finger located adequately distend the bladder by this approach. For these pa-
in the vagina at the palpated site of the urethral meatus may tients, ultrasonography is used to locate the bladder and allow
be successful. the insertion of a 22-gauge spinal needle. Saline is instilled into
When urologic consultation is obtained, other techniques the bladder via the needle to distend the bladder enough for
for urethral catheterization can be used. Flexible cystoscopy suprapubic tube placement (Fig. 18.1).
may be performed to ascertain the reason for difficult catheter In patients with previous lower abdominal surgery, ultra-
placement and for insertion of a guidewire. A urethral catheter sonographic guidance is often necessary before a percutaneous
can then be placed over the guidewire by the Seldinger tech- cystotomy can be performed safely. Previous surgery can lead
nique. Filiforms and followers are useful for urethral strictures. to adhesions that can hold a loop of intestine in the area of in-
sertion. Other relative contraindications include patients with
coagulopathy, a known history of bladder tumors, or active
Indications hematuria and retained clots. In patients with bladder tumors,
percutaneous bladder access should be avoided because tumor
On occasion, despite proper technique (as outlined previ- cell seeding can occur along the percutaneous tract. Suprapu-
ously), urethral catheterization is unsuccessful. These are the bic cystotomy tubes are small in caliber and therefore do not
instances when percutaneous suprapubic cystotomy is neces- function effectively with severe hematuria and retained clots.
sary. Undoubtedly, the most common indication for percuta- Instead, open surgical placement of a large-caliber tube is nec-
neous suprapubic cystotomy is for the management of acute essary if urethral catheterization is impossible.
urinary retention in men. Other indications for a percutaneous
suprapubic cystotomy in the intensive care unit are provided
in Table 18.1. Technique
There are two general types of percutaneous cystotomy tubes
Contraindications that range in size from 8 to 14 Fr [5,6]. The first type uses
an obturator with a preloaded catheter. Examples include the
The contraindications to percutaneous suprapubic cystotomy Stamey catheter (Cook Urological, Spencer, IN) and the Bo-
are provided in Table 18.2. An inability to palpate the bladder nanno catheter (Beckton Dickinson and Co, Franklin Lakes,
or distortion of the pelvic anatomy from previous surgery or NJ) [7]. The Stamey device is a polyethylene Malecot catheter
trauma makes percutaneous entry of the bladder difficult. In with a luer lock hub that fits over a hollow needle obturator
these situations, the risks of penetrating the peritoneal cavity (Fig. 18.2A). When the obturator is locked to the hub of the
become substantial. The bladder may not be palpable if the pa- catheter, the Malecot flanges are pulled inward (closed) and
tient is in acute renal failure with oliguria or anuria, has a small the system is ready for use. The Bonanno catheter uses a flexi-
contracted neurogenic bladder, or is incontinent. When the ble 14-Fr Teflon tube, which is inserted over a hollow 18-gauge
bladder is not palpable, it can be filled in a retrograde manner obturator (Fig. 18.2B). The obturator locks into the catheter
hub and extends beyond the catheter tip. When the obturator
is withdrawn, the tube pigtails in the bladder. One advantage
TA B L E 1 8 . 1 to the Stamey catheter is that the flanges provide a secure re-
taining system. The Bonanno catheter generally induces fewer
COMMON INDICATIONS FOR PERCUTANEOUS bladder spasms, however, and is better tolerated.
CYSTOTOMY The second type of percutaneous cystotomy tube consists of
a trocar and sheath, which are used to penetrate the abdominal
Unsuccessful urethral catheterization in the setting of acute wall and bladder [8,9]. One of the most popular systems is the
urinary retention Lawrence suprapubic catheter (Rusch, Duluth, GA). This sys-
History of prostate surgery tem allows a standard Foley catheter to be placed after removal
Presence or suspected urethral trauma of the trocar (Fig. 18.2C).
Urethral stricture The patient is placed in the supine position; a towel roll
Severe hypospadias may be placed under the hips to extend the pelvis. Trende-
Periurethral abscess lenburg position may help to move the abdominal contents
Presence of severe urethral, epididymal, or prostate infection away from the bladder. The bladder is palpated to ensure that
it is distended. The suprapubic region is prepared with 2%
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152 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

Inability to place
Uretheral catheter

No
Retrograde
Bladder adequately filled
Bladder filling

Previous abdominal
Surgery

Yes No

Ultrasoundguided needle Spinal needle and


localization and suprapubic suprapubic tube
tube placement. placement.
FIGURE 18.1. Algorithm for percutaneous suprapubic
tube placement.

chlorhexidine/10% povidoneiodine solution and draped with the suprapubic crease, where the fat thickness is minimal. One
sterile towels. The insertion site is several centimeters above percent lidocaine is used to anesthetize the skin, subcutaneous
the symphysis pubis in the midline: this approach avoids the tissues, rectus fascia, and retropubic space. A 22-gauge spinal
epigastric vessels. In obese patients with a large abdominal fat needle with a 5-mL syringe is directed vertically and advanced
pad, the fold is elevated. The needle should be introduced into until urine is aspirated. If the bladder is smaller or the patient
had previous pelvic surgery, the needle is directed at a 60-degree
caudal angle. Insertion of the cystotomy tube is predicated on
the feasibility of bladder puncture and after the angle and depth
of insertion are established with the spinal needle (Fig. 18.3).
At the site of bladder puncture, a small 2-mm incision is
made with a no. 11 blade. The catheter mounted on the ob-
turator is advanced into the bladder. Two hands are used to
grasp the system to provide a forceful, but controlled, thrust
through the abdominal wall. One hand can be positioned on
A the obturator at a site marking the depth of the bladder. A
syringe attached to the end of the obturator is used to aspi-
rate urine and confirm obturator placement. Once the bladder
is penetrated, the entire system is advanced 2 to 3 cm. This
prevents the catheter tip from withdrawing into the retropubic
space when the bladder decompresses. After unlocking the ob-
turator from the catheter, the obturator acts as a guide while
the catheter is advanced into the bladder. When using a Stamey
B catheter, the catheter can be gently withdrawn until the Malecot
flanges meet resistance against the anterior bladder wall. The
Stamey catheter is then advanced 2 cm back into the bladder
to allow for movement. This maneuver pulls the catheter away
from the bladder trigone and helps reduce bladder spasms.
The same general technique applies to placement of the
Lawrence suprapubic catheter system. After the bladder is pen-
etrated, urine appears at the hub of the suprapubic catheter in-
C troducer (trocar plus sheath). The trocar is then removed and a
FIGURE 18.2. A: Stamey suprapubic cystostomy trocar set (A is the Foley catheter is inserted. The Foley catheter balloon is inflated
obturator, B is the Malecot catheter, and C is the drainage tube). to secure it in the bladder. Pulling the tab at the top of the peel-
B: Bonanno catheter set (A is the obturator and B is the catheter). away sheath allows the remaining portion of the sheath to be
C: Lawrence suprapubic catheter (A is the trocar and B is the sheath). removed away from the catheter.
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Chapter 18: Percutaneous Suprapubic Cystostomy 153

FIGURE 18.4. Ultrasound image of full bladder.

SUPRAPUBIC CATHETER CARE


Bladder spasms occur commonly after suprapubic catheter
B placement. When using a Stamey catheter or a Foley catheter,
bladder spasms can be prevented by withdrawing the tube until
FIGURE 18.3. Technique of suprapubic trocar placement. A: Area to it meets the anterior bladder wall and then advancing 2 cm back
be shaved, prepared, and draped before trocar placement. B: Position into the bladder. Persistent bladder spasms can be treated with
of the Stamey trocar in the bladder. The angle, distance from the pu- anticholinergic therapy (e.g., oxybutynin and hyoscyamine).
bis, and position of the catheter in relation to the bladder wall are
demonstrated.
This medication should be discontinued before removing the
suprapubic tube to prevent urinary retention.
A suprapubic tube that ceases to drain is usually caused
by kinking of the catheter or displacement of the catheter tip
The patency of the catheter is assessed by irrigating the blad- into the retropubic space. If necessary, suprapubic catheters
der after decompression. The catheter can be fixed with a sim- may be replaced either by using an exchange set (available for
ple nylon suture and sterile dressing. The Bonanno catheter Stamey catheters) or by dilating the cystotomy tract. Closure of
contains a suture disk. The Lawrence suprapubic catheter does the percutaneous cystotomy tract is generally prompt after the
not require extra fixation because the balloon on the Foley tube is removed. Prolonged suprapubic tube use can lead to a
catheter secures it in place. mature tract, which may take several days to close. If the tract
remains open, bladder decompression via a urethral catheter
may be required.

IMAGE-GUIDED PERCUTANEOUS
SUPRAPUBIC CYSTOSTOMY COMPLICATIONS
Ultrasound provides physicians with a twofold increase in suc- Placement of suprapubic cystotomy tubes is generally safe with
cess rates for suprapubic bladder needle aspiration and was infrequent complications. Possible complications are provided
sensitive in evaluating and confirming bladder distention [10]. in Table 18.3 [13]. Bowel complications are severe, but rare,
It is readily available, can be performed at the bedside, is easy with this procedure [14]. Penetration of the peritoneal cavity
to perform, and poses no additional risk to the patient [11,12]. or bowel perforation produces peritoneal or intestinal symp-
Ultrasound visualization of a full bladder is easy to learn and toms and signs. This complication may be avoided by attempt-
provides a well-defined image of the bladder (Fig. 18.4). The ing the procedure on well-distended bladders, using a midline
bladder is located beneath the abdominal muscles in the lower
midline position, anterior to the uterus in females. A full blad-
der is easy to visualize as a midline symmetrical hypoechoic TA B L E 1 8 . 3
image under the abdominal rectus muscles in the suprapubic
abdominal region. The bladder is best visualized when it is COMPLICATIONS OF PERCUTANEOUS CYSTOTOMY
distended, using 3.5-, 5.0-, or 7.5-MHz transducer probes on
transabdominal transverse and longitudinal axial planes. Ul- Peritoneal and bowel perforation
trasound can establish the presence of fluid in and surround- Hematuria
ing the bladder, as well as provide dimensions of depth and Retained or calcified catheter
size of the bladder itself. Tenting of the bladder wall can be Bladder stones
seen by ultrasound as the needle pushes against the bladder be- Postobstructive diuresis
fore penetration occurs and the catheter can be seen within Hypotension
the bladder once the cystostomy tube placement has been Bladder perforation and infection of space of Retzius
performed.
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154 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

Entrapped bowel

FIGURE 18.5. Placement of the suprapubic


tube can perforate entrapped bowel.

approach no more than 4 cm above the pubis or under image Complications associated with the catheter include loss
guidance. of a portion of the catheter in the bladder, calcification of
In patients who have had previous lower abdominal or the catheter, or bladder stone formation. These complications
pelvic surgery, an ultrasound may be used to properly place may be avoided by preventing prolonged catheter use. Beyond
the suprapubic tube and rule out entrapped bowel (Fig. 18.5). 4 weeks, evaluation and replacement or removal of catheter is
Patients who develop peritoneal symptoms and signs require a advisable.
full evaluation of the location of not only the suprapubic tube When chronically distended bladders are decompressed, pa-
(by a cystogram) but also the cystotomy tract. A kidneyureter tients are at risk for postobstructive diuresis [15]. Patients who
bladder radiograph and computed tomography scans may be are at greatest risk include those with azotemia, peripheral
helpful. edema, congestive heart failure, and mental status changes.
Hematuria is the most common complication after supra- Patients with postobstructive diuresis (i.e., urine outputs
pubic tube placement. Rarely, this requires open cystotomy for >200 mL per hour) require frequent monitoring of vital signs
placement of a large-caliber tube for irrigation. Hematuria can and intravenous fluid replacement.
result secondary to laceration of blood vessels or rapid de- Hypotension rarely occurs after suprapubic tube placement.
compression of a chronically distended bladder, and the risk It may be caused by a vasovagal response or bleeding, allevi-
of hematuria may be reduced by gradual bladder decompres- ated by fluid administration. Another rare, but possible, com-
sion. Another risk with decompression of chronically distend plication is a through-and-through bladder perforation that is
bladder is postobstructive diuresis. treated conservatively with bladder decompression.

References
1. Hodgkinson CP, Hodari AA: Trocar suprapubic cystostomy for postopera- 9. Chiou RK, Morton JJ, Engelsgjerd JS, et al: Placement of large suprapubic
tive bladder drainage in the female. Am J Obstet Gynecol 96(6):773783, tube using peel-away introducer. J Urol 153(4):11791181, 1995.
1966. 10. Munir V, Barnett P, South M: Does the use of volumetric bladder ultrasound
2. Wein AJ, Kavoussi LR, Novick AC, et al: Campbell-Walsh Urology Ninth improve the success rate of suprapubic aspiration of urine? Pediatr Emerg
Edition Review. Philadelphia, PA, Saunders/Elsevier, 2007. Care 18(5):346, 2002.
3. Brosnahan J, Jull A, Tracy C: Types of urethral catheters for management of 11. Aguilera PA, Choi T, Durham BA: Ultrasound-guided suprapubic cystostomy
short-term voiding problems in hospitalised adults. Cochrane Database Syst catheter placement in the emergency department. J Emerg Med 26(3):319
Rev (1):Cd004013, 2004. 321, 2004.
4. Siderias J, Guadio F, Singer AJ: Comparison of topical anesthetics and lu- 12. Lee MJ, Papanicolaou N, Nocks BN, et al: Fluoroscopically guided percuta-
bricants prior to urethral catheterization in males: a randomized controlled neous suprapubic cystostomy for long-term bladder drainage: an alternative
trial. Acad Emerg Med 11(6):703706, 2004. to surgical cystostomy. Radiology 188(3):787789, 1993.
5. Irby Iii P, Stoller M: Percutaneous suprapubic cystostomy. J Endourol 13. Dogra P, Goel R: Complication of percutaneous suprapubic cystostomy. Int
7(2):125130, 1993. Urol Nephrol 36(3):343344, 2004.
6. Lawrentschuk N, Lee D, Marriott P, et al: Suprapubic stab cystostomy: a 14. Liau S, Shabeer U: Laparoscopic management of cecal injury from a mis-
safer technique. Urology 62(5):932934, 2003. placed percutaneous suprapubic cystostomy. Surg Laparosc Endosc Percutan
7. Bonanno PJ, Landers DE, Rock DE: Bladder drainage with the suprapubic Tech 15(6):378, 2005.
catheter needle. Obstet Gynecol 35(5):807812, 1970. 15. Nyman MA, Schwenk NM, Silverstein MD: Management of urinary reten-
8. Obrien WM, Pahira JJ: Percutaneous placement of suprapubic tube using tion: rapid versus gradual decompression and risk of complications. Mayo
peel-away sheath introducer. Urology 31(6):524525, 1988. Clin Proc 72(10):951956, 1997.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 19: Aspiration of the Knee and Synovial Fluid Analysis 155

CHAPTER 19 ASPIRATION OF THE KNEE


AND SYNOVIAL FLUID ANALYSIS
BONNIE J. BIDINGER AND ERIC W. JACOBSON

Arthrocentesis is a safe and relatively simple procedure that in- lateral joint line. If a bulge of fluid is noted at the medial joint
volves the introduction of a needle into a joint space to remove line, a small effusion is present (Fig. 19.1). If a large effusion is
synovial fluid. It constitutes an essential part of the evaluation present, one can detect a ballotable patella by pushing it against
of arthritis of unknown cause, frequently with the intent to rule the femur with the right index finger while applying pressure to
out a septic process [13]. the suprapatellar pouch with the left hand [13]. Comparison
Ropes and Bauer [4] first categorized synovial fluid as in- with the opposite joint is helpful. Many texts describe joint
flammatory or noninflammatory in 1953. In 1961, Hollander examination and assessment for fluid in the knee and other
et al. [5] and Gatter and McCarty [6] coined the term syn- joints [1113].
ovianalysis to describe the process of joint fluid analysis and
were instrumental in establishing its critical role in the diag-
nosis of certain forms of arthritis. Septic arthritis and crys-
talline arthritis can be diagnosed by synovial fluid analysis
alone. They may present similarly but require markedly dif- CONTRAINDICATIONS
ferent treatments, thus necessitating early arthrocentesis and
Absolute contraindications to arthrocentesis include local in-
prompt synovial fluid analysis.
fection of the overlying skin or other periarticular structures
and severe coagulopathy [13,10]. If coagulopathy is present
and septic arthritis is suspected, every effort should be made
to correct the coagulopathy (with fresh-frozen plasma or al-
INDICATIONS ternate factors) before joint aspiration. Therapeutic anticoag-
ulation is not an absolute contraindication, but every effort
Arthrocentesis is performed for diagnostic and therapeutic pur-
should be made to avoid excessive trauma during aspiration
poses. The main indication for arthrocentesis is to assist in
in this circumstance. Known bacteremia is a contraindication
the evaluation of arthritis of unknown cause. In the intensive
because inserting a needle into the joint space disrupts capil-
care unit, it is most commonly performed to rule out septic
lary integrity, allowing joint space seeding [14]. However, if
arthritis. As many types of inflammatory arthritis mimic sep-
septic arthritis is strongly suspected, joint aspiration is indi-
tic arthritis, synovial fluid analysis is essential in differentiat-
cated. The presence of articular instability (e.g., that seen with
ing the various causes of inflammatory arthritis [4,7] (Table
badly damaged joints) is a relative contraindication, although
19.1). Therefore, patients presenting with acute monoarthri-
the presence of a large presumed inflammatory fluid may still
tis or oligoarthritis require prompt arthrocentesis with sub-
warrant joint aspiration.
sequent synovial fluid analysis, preferably before initiation of
treatment.
Arthrocentesis is also used for therapeutic purposes. In a
septic joint, serial joint aspirations are required to remove ac-
cumulated inflammatory or purulent fluid. This accomplishes COMPLICATIONS
complete drainage of a closed space and allows serial mon-
itoring of the total white blood cell count, Gram stain, and The major complications of arthrocentesis are iatrogenically in-
culture to assess treatment response. Inflammatory fluid con- duced infection and bleeding, both of which are extremely rare
tains many destructive enzymes that contribute to cartilage [1]. The risk of infection after arthrocentesis has been estimated
and bony degradation; removal of the fluid may slow this to be less than 1 in 10,000 [15]. Hollander [16] reported an
destructive process [8,9]. Additionally, arthrocentesis allows incidence of less than 0.005% in 400,000 injections. Strict ad-
for injection of long-acting corticosteroid preparations into herence to aseptic technique reduces the risk of postarthrocen-
the joint space, which may be a useful treatment for var- tesis infection. Significant hemorrhage is also extremely rare.
ious inflammatory and noninflammatory forms of arthritis Correction of prominent coagulopathy before arthrocentesis
[10]. reduces this risk.
Before performing arthrocentesis, it must be ascertained Another potential complication of arthrocentesis is direct
that the true joint is inflamed and an effusion is present. This injury to the articular cartilage by the needle. This is not quan-
requires a meticulous physical examination to differentiate tifiable, but any injury to the cartilage could be associated with
arthritis from periarticular inflammation. Bursitis, tendinitis, degenerative change over time. To avoid cartilaginous dam-
and cellulitis all may mimic arthritis. In the knee, the exami- age, the needle should be pushed in only as far as necessary to
nation begins with assessment of swelling. A true effusion may obtain fluid and excessive movement of the needle during the
cause bulging of the parapatellar gutters and the suprapatellar procedure should be avoided.
pouch [11]. The swelling should be confined to the joint space. Other complications include discomfort from the procedure
To check for small effusions, the bulge test is performed [12]. itself, allergic reactions to the skin preparation or local anes-
Fluid is stroked from the medial joint line into the suprapatellar thetic, and in the case of steroid injection, postinjection flare
pouch and then from the suprapatellar pouch down along the and local soft-tissue atrophy from the glucocorticoid [17].
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156 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 1 9 . 1 TA B L E 1 9 . 2
COMMON CAUSES OF NONINFLAMMATORY AND ARTHROCENTESIS EQUIPMENT
INFLAMMATORY ARTHRITIDES
Procedure Equipment
Noninflammatory Inflammatory
Skin preparation and 2% chlorhexidine in 70% isopropyl
Osteoarthritis Rheumatoid arthritis local anesthesia alcohol
Trauma/internal derangement Spondyloarthropathies Ethyl chloride spray
Avascular necrosis Psoriatic arthritis For local anesthesia1% lidocaine;
Hemarthrosis Reiters syndrome/reactive 25-gauge, 1.5-in needle; 22-gauge,
Malignancy arthritis 1.5-in. needle; 5-mL syringe
Benign tumors Ankylosing spondylitis Sterile sponge/cloth
Osteochondroma Ulcerative colitis/regional Arthrocentesis Gloves
Pigmented villonodular enteritis 20- to 60-mL syringe (depending on
synovitis size of effusion)
Crystal-induced arthritis
Monosodium urate (gout) 18- to 22-gauge, 1.5-in. needle
Calcium pyrophosphate Sterile sponge/cloth
dihydrate (pseudogout) Sterile clamp
Hydroxyapatite Sterile bandage
Infectious arthritis Collection 15-mL anticoagulated tube (with
Bacterial sodium heparin or ethylene-
Mycobacterial diaminetetraacetic acid)
Fungal Sterile tubes for routine cultures
Connective tissue diseases Slide, cover slip
Systemic lupus
erythematosus
Vasculitis
Scleroderma
Polymyositis are quite difficult to enter blindly and are more appropriately
Hypersensitivity entered using radiologic guidance, such as with fluoroscopy or
Serum sickness computed tomography; these include the hip, sacroiliac, and
temporomandibular joints. Many texts describe in detail the
aspiration technique of other joints [3,1618]. The technique
for knee aspiration is as follows:

TECHNIQUE 1. Describe the procedure to the patient, including the possi-


ble complications, and obtain written informed consent.
Joint aspiration is easily learned. A sound knowledge of the 2. Collect all items needed for the procedure (Table 19.2).
joint anatomy, including the bony and soft-tissue landmarks 3. With the patient supine and the knee fully extended, ex-
used for joint entry, is needed. Strict aseptic technique must amine the knee to confirm the presence of an effusion, as
be followed to minimize risk of infection, and relaxation of described previously.
the muscles surrounding the joint should be encouraged be- 4. Identify landmarks for needle entry. The knee may be as-
cause muscular contraction can impede the needles entry into pirated from a medial or lateral approach. The medial ap-
the joint. proach is more commonly used and is preferred when small
Most physicians in the intensive care unit can aspirate the effusions are present. Identify the superior and inferior bor-
knee because it is one of the most accessible joints. Other joints ders of the patella. Entry should be halfway between the
should probably be aspirated by an appropriate specialist, such borders, just inferior to the undersurface of the patella (Fig.
as a rheumatologist or an orthopedic surgeon. Certain joints 19.2). The entry site may be marked with pressure from

FIGURE 19.1. The bulge test. A:


Milk fluid from the suprapatellar
pouch into the joint. B: Slide the hand
down the lateral aspect of the joint line
A B and watch for a bulge medial to the
joint.
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Chapter 19: Aspiration of the Knee and Synovial Fluid Analysis 157

perpetuate an inflammatory or destructive process. If the


syringe is full and more fluid remains, a sterile hemostat
may be used to clamp the needle, thus stabilizing it, while
switching syringes. When the syringes have been switched,
more fluid can be withdrawn. The syringes must be sterile.
8. On occasion, effusions can be difficult to aspirate. Reasons
for this include increased fluid viscosity, fibrin and other de-
bris impeding flow through the needle, loculated fluid, and
use of a needle with an inappropriately small gauge. Ad-
ditionally, the fluid may not be accessible by the approach
being used [19]. At times, one can obtain a small drop
of joint fluid by using continuous suction as the needle is
withdrawn from the joint space [17]. This small specimen
can then be sent for Gram stain, culture, and if possible,
crystal analysis.
9. When the fluid has been obtained, quickly remove the nee-
dle and apply pressure to the needle site with a piece of ster-
ile gauze. When bleeding has stopped, remove the gauze,
clean the area with alcohol, and apply an adhesive ban-
FIGURE 19.2. Technique of aspirating the knee joint. The needle en- dage. If the patient is receiving anticoagulation therapy or
ters halfway between the superior and inferior borders of the patella has a bleeding diathesis, apply prolonged pressure.
and is directed just inferior to the patella. 10. Document the amount of fluid obtained and perform gross
examination, noting the color and clarity. A string sign
may be performed at the bedside to assess fluid viscosity
(see the following section). Send fluid for cell count with
the end of a ballpoint pen with the writing tip retracted.
differential count, Gram stain, routine culture, specialized
An indentation mark should be visible.
cultures for Gonococcus, Mycobacterium, and fungus, if
5. Cleanse the area with 2% chlorhexidine in 70% iso-
indicated, and polarized microscopic examination for crys-
propyl alcohol and allow the area to dry. Practice universal
tal analysis. Other tests, such as glucose and complement
precautions: wear gloves at all times while handling any
determinations, are generally not helpful. Use an anticoag-
body fluid, although they need not be sterile for routine
ulated tube to send fluid for cell count and crystal analysis.
knee aspiration. Do not touch the targeted area once it has
Sodium heparin and ethylenediaminetetraacetic acid are
been cleaned.
appropriate anticoagulants. Lithium heparin and calcium
6. Apply local anesthesia. A local anesthetic (1% lidocaine)
oxalate should be avoided because they can precipitate out
may be instilled subcutaneously with a 25-gauge, 1.5-in.
of solution to form crystals, thus potentially giving a false-
needle. Once numbing has occurred, deeper instillation of
positive assessment for crystals [6,20]. Fluid may be sent
the local anesthetic to the joint capsule can be performed.
for Gram stain and culture in the syringe capped with a
Some physicians may use ethyl chloride as an alternative
blunt tip or in a sterile redtop tube.
anesthetic. However, this agent provides only superficial
anesthesia of the skin. To use, spray ethyl chloride directly
onto the designated area and stop when the first signs of
freezing are evident in order to limit potential for skin dam-
age. SYNOVIAL FLUID ANALYSIS
7. To enter the knee joint, use an 18- to 22-gauge, 1.5-in. nee-
dle with a 20- to 60-mL syringe. Use a larger gauge needle Synovial fluid analysis is identical for all joints and begins with
particularly if septic arthritis is suspected as the aspirated bedside observation of the fluid. The color, clarity, and viscos-
fluid may be purulent and more difficult to aspirate. Use ity of the fluid are characterized. Synovial fluid is divided into
a quick thrust through the skin and on through the cap- noninflammatory and inflammatory types on the basis of the
sule to minimize pain. Avoid hitting periosteal bone, which total nucleated cell count. A white blood cell count less than
causes significant pain, or cartilage, which causes cartilagi- or equal to 2,000 per L indicates a noninflammatory fluid
nous damage. Aspirate fluid to fill the syringe. If the fluid and a count greater than 2,000 per L indicates an inflamma-
appears purulent or hemorrhagic, try to tap the joint dry, tory fluid. Table 19.3 shows how fluid is divided into major
which will remove mediators of inflammation that may categories on the basis of appearance and cell count.

TA B L E 1 9 . 3
JOINT FLUID CHARACTERISTICS

Characteristic Normal Noninflammatory Inflammatory Septic

Color Clear Yellow Yellow or opalescent Variablemay be purulent


Clarity Transparent Transparent Translucent Opaque
Viscosity Very high High Low Typically low
Mucin clot Firm Firm Friable Friable
White blood cell count per L 200 2002,000 2,000100,000 >50,000, usually >100,000
Polymorphonuclear cells (%) <25 <25 >50 >75
Culture Negative Negative Negative Usually positive
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158 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

it drops off the end of the needle or syringe like water dropping
GROSS EXAMINATION from a faucet.
The mucin clot, another measure of viscosity, estimates the
Color presence of intact hyaluronic acid and hyaluronic acidprotein
interactions. This test is performed by placing several drops of
Color and clarity should be tested using a clear glass tube. synovial fluid in 5% acetic acid and then mixing with a stirring
Translucent plastic, as used in most disposable syringes, in- stick. A good mucin clot forms in normal, noninflammatory
terferes with proper assessment [1]. Normal synovial fluid is fluid. The fluid remains condensed in a clot resembling chewed
colorless. Noninflammatory and inflammatory synovial fluid gum. A poor mucin clot is seen with inflammatory fluid; the
appears yellow or straw colored. Septic effusions frequently ap- fluid disperses diffusely within the acetic acid.
pear purulent and whitish. Depending on the number of white
blood cells present, pure pus may be extracted from a sep-
tic joint. Hemorrhagic effusions appear red or brown. If the CELL COUNT AND DIFFERENTIAL
fluid looks like pure blood, the tap may have aspirated venous
blood. The needle is removed, pressure is applied, and the joint The cell count should be obtained as soon as possible after
is reentered from an alternate site. If the same bloody appear- arthrocentesis, as a delay of even several hours may cause an
ance is noted, the fluid is a hemorrhagic effusion and probably artificially low white blood cell count [21]. The total white
not related to the trauma of the aspiration. If any question re- blood cell count of synovial fluid differentiates noninflamma-
mains, the hematocrit of the effusion is compared with that of tory from inflammatory fluid, as noted previously. In general,
peripheral blood. The hematocrit in a hemorrhagic effusion is the higher the total white blood cell count, the more likely
typically lower than that of peripheral blood. In the case of a the joint is to be infected. This is not absolute, however, and
traumatic tap, the hematocrit of the fluid should be equal to there is considerable overlap. For instance, a total white cell
that of peripheral blood. For causes of a hemorrhagic effusion, count greater than 100,000 per L may be seen in conditions
refer to Table 19.4. other than infection, whereas a total white blood cell count of
50,000 per L may be due to infection, crystalline disease, or
systemic inflammatory arthropathy [28]. The technique for the
cell count is identical to that used with peripheral blood. The
Clarity fluid may be diluted with normal saline for a manual count, or
an automated counter may be used. Viscous fluid with exces-
The clarity of synovial fluid depends on the number and types
sive debris may clog a counter or give falsely elevated results,
of cells or particles present. Clarity is tested by reading black
thus making the manual procedure somewhat more accurate.
print on a white background through a glass tube filled with the
The differential white blood cell count is also performed
synovial fluid. If the print is easily read, the fluid is transparent.
using the technique used for peripheral blood, typically using
This is typical of normal and noninflammatory synovial fluid.
Wrights stain. The differential is calculated on the basis of
If the black print can be distinguished from the white back-
direct visualization. The differential count includes cells typi-
ground, but is not clear, the fluid is translucent. This is typical
cally seen in peripheral blood, such as polymorphonuclear cells,
of inflammatory effusions. If nothing can be seen through the
monocytes, and lymphocytes, as well as cells localized to the
fluid, it is opaque. This occurs with grossly inflammatory, sep-
synovial space. In general, the total white blood cell count and
tic, and hemorrhagic fluids.
the polymorphonuclear cell count increase with inflammation
and infection. Septic fluid typically has a differential of greater
than 75% polymorphonuclear cells (see Table 19.3).
Viscosity In addition to distinguishing polymorphonuclear cells from
monocytes and lymphocytes, Wrights stain can detect other
The viscosity of synovial fluid is a measure of the hyaluronic cells in synovial fluid that can be useful in establishing a diag-
acid content. Degradative enzymes such as hyaluronidase nosis. For instance, iron-laden chondrocytes, which are seen in
are released in inflammatory conditions, thus destroying hemochromatosis, may be picked up by Wrights stain, as may
hyaluronic acid and other proteinaceous material, resulting in be fat droplets and bone marrow spicules, which are suggestive
a thinner, less viscous fluid. Highly viscous fluid, on the other of trauma or a fracture into the joint [19].
hand, can be seen in myxedematous or hypothyroid effusions.
Viscosity can be assessed at the bedside using the string sign
[1]. A drop of fluid is allowed to fall from the end of the needle CRYSTALS
or syringe and the length of the continuous string that forms is
estimated. Normal fluid typically forms at least a 6-cm contin- All fluid should be assessed for the presence of crystals. As
uous string. Inflammatory fluid does not form a string; instead, with cell count, crystal analysis should be performed as soon
as possible after arthrocentesis. A delay is associated with a
decreased yield [21]. One drop of fluid is placed on a slide and
TA B L E 1 9 . 4 covered with a coverslip; this is examined for crystals using
a compensated polarized light microscope. The presence of
CAUSES OF A HEMORRHAGIC EFFUSION intracellular monosodium urate (MSU) or calcium pyrophos-
phate dihydrate (CPPD) crystals confirms a diagnosis of gout or
Trauma (with or without fracture) pseudogout, respectively. MSU crystals are typically long and
Hemophilia and other bleeding disorders needle shaped: they may appear to pierce through a white blood
Anticoagulant therapy cell. The crystals are strongly negatively birefringent, appear-
Tumor (metastatic and local) ing yellow when parallel to the plane of reference. Typically,
Hemangioma CPPD crystals are small and rhomboid. The crystals are weakly
Pigmented villonodular synovitis positively birefringent, appearing blue when oriented parallel
Ehlers-Danlos syndrome to the plane of reference. Rotating the stage of the microscope
Scurvy by 90 degrees and thereby the orientation of the crystals (now
perpendicular to the plane of reference) changes their color:
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Chapter 19: Aspiration of the Knee and Synovial Fluid Analysis 159

TA B L E 1 9 . 5 reveals characteristic bipyramidal crystals as well as polymor-


phic forms [22].
CLASSIFICATION OF HYPERURICEMIA The yield for all crystals can be increased by spinning the
specimen and examining the sediment. If the fluid cannot be
Primary hyperuricemia examined immediately, it should be refrigerated to preserve
Idiopathic the crystals. It is important to note that even in the presence of
Enzymatic defects (e.g., hypoxanthine guanine crystals, infection must be considered because crystals can be
phosphoribosyl- transferase deficiency) seen concomitantly with a septic joint.
Secondary hyperuricemia Other crystals include cryoimmunoglobulins in patients
Increased production of uric acid with multiple myeloma and essential cryoglobulinemia [27],
Increased de novo purine synthesis and cholesterol crystals in patients with chronic inflammatory
Excessive dietary purine intake arthropathies, such as rheumatoid arthritis. Cholesterol crys-
Increased nucleic acid turnover (myeloproliferative/ tals are a nonspecific finding and appear as platelike structures
lymphoproliferative disorders, psoriasis, hemolytic with a notched corner.
anemia, ethyl alcohol abuse)
Decreased renal excretion of uric acid
Medications
Diuretics
GRAM STAIN AND CULTURE
Low-dose salicylates
The Gram stain is performed as with other body fluids. It
Pyrazinamide
should be performed as soon as possible to screen for the pres-
Ethambutol
ence of bacteria. It has been reported that the sensitivity of
Cyclosporine
synovial fluid Gram stain in septic arthritis ranges between
Chronic renal failure 50% and 75% for nongonococcal infection and less than 10%
Hyperacidemia (lactic acidosis, ketoacidosis, starvation, ethyl for gonococcal infection [28]. Specificity is much higher; this
alchohol abuse) suggests that a positive Gram stain, despite a negative culture,
Lead nephropathy should be considered evidence of infection. In fact, it is not un-
common for only the Gram stain to be positive in the setting of
infection [28]. However, the absence of bacteria by the Gram
stain does not rule out a septic process.
Synovial fluid in general should be cultured routinely for aer-
MSU crystals turn blue and CPPD crystals turn yellow. Refer
obic and anaerobic bacterial organisms. A positive culture con-
to Tables 19.5 and 19.6 for a classification of hyperuricemia
firms septic arthritis. In certain circumstances (e.g., in chronic
and conditions associated with CPPD deposition disease.
monoarticular arthritis), fluid may be cultured for the pres-
In addition to MSU and CPPD crystals, other less com-
ence of mycobacteria, fungus, and spirochetes. If disseminated
mon crystals may induce an inflammatory arthropathy. Basic
gonorrhea is suspected, the laboratory must be notified be-
calcium crystals (e.g., hydroxyapatite) and oxalate crystals
cause the fluid should be plated directly onto chocolate agar
are two such types. Much like MSU crystals in gout, hy-
or ThayerMartin medium. Just as Gram stain of synovial
droxyapatite crystals can incite acute articular and periartic-
fluid in gonococcal infection is often negative, so too is syn-
ular inflammation, which can be difficult to distinguish clini-
ovial fluid culture. Synovial fluid culture is positive approx-
cally from septic arthritis and cellulitis, respectively [22]. On
imately 10% to 50% of the time, versus 75% to 95% of
light microscopy, however, crystals appear as clumps of shiny
the time for nongonococcal infection [28]. However, cultures
nonbirefringent globules, and with alizarin red S stain, the
of genitourinary sites and mucosal sites in gonococcal infec-
clumps appear red-orange [22,23]. If hydroxyapatite is sus-
tion are positive approximately 80% of the time [29]. There-
pected, alizarin red S stain must be requested specifically from
fore, when suspicion of gonococcal arthritis is high (e.g., in a
the laboratory as it is not a routine component of the crystal
young, healthy, sexually active individual with a dermatitis-
analysis. Calcium oxalate crystals can also induce an inflam-
arthritis syndrome), the diagnosis must often be confirmed
matory arthritis. This is generally seen in patients on long-
by a positive culture from the urethra, cervix, rectum, or
term hemodialysis [2426], but may also be seen in young
pharynx.
patients with primary oxalosis [22]. Synovial fluid typically
In addition to documenting infection and identifying a spe-
cific organism, synovial fluid culture can be useful in deter-
mining antibiotic sensitivities and subsequent treatment. Fur-
TA B L E 1 9 . 6 thermore, serial synovial fluid cultures can help in assessing
response to therapy. For example, a negative follow-up culture
CONDITIONS ASSOCIATED WITH CALCIUM associated with a decrease in synovial fluid polymorphonuclear
PYROPHOSPHATE DIHYDRATE DEPOSITION DISEASE cell count is highly suggestive of improvement.
Other studies on synovial fluid (e.g., glucose, protein, lac-
Hereditary tate dehydrogenase, complement, and immune complexes) are
Sporadic (idiopathic) generally not helpful. Specifically, in a study by Shmerling
Aging et al. [30], the investigators observed that synovial fluid glu-
Metabolic diseases cose and protein were highly inaccurate. The synovial fluid
Hyperparathyroidism glucose and protein misclassified effusions as inflammatory
Hypothyroidism versus noninflammatory 50% of the time. By contrast, syn-
Hypophosphatemia ovial fluid cell count and differential were found to be re-
Hypomagnesemia liable and complementary; sensitivity and specificity of cell
Hemochromatosis count was 84% for both and for the differential was 75%
Amyloidosis and 92%, respectively [30]. Although synovial fluid lactate de-
Trauma hydrogenase was also found to be accurate, it did not offer
any additional information above and beyond the cell count
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160 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

and differential. A more recent critical appraisal of synovial Of note, there are special stains for synovial fluid that can
fluid analysis was conducted by Swan et al. [31] in 2002. be helpful as the clinical picture warrants; these include Congo
Through a detailed survey of the literature, the authors con- red staining for amyloid arthropathy. Amyloid deposits display
firmed the diagnostic value of synovial fluid analysis in cases an apple-green birefringence with polarized light [32]. Prussian
of acute arthritis when an infectious or crystalline etiology is blue stain for iron deposition may reveal iron in synovial lin-
suspected, as well as in cases of intercritical gout. The useful- ing cells in hemochromatosis [19]. However, neither of these
ness of other synovial fluid assays was not supported by the studies should be considered a routine component of synovial
literature. fluid analysis.

References
1. Gatter RA: A Practical Handbook of Joint Fluid Analysis. Philadelphia, Lea 18. Canoso JJ: Aspiration and injection of joints and periarticular tissues, in
& Febiger, 1984. Hochberg MC, Silman AJ, Smolen JS, et al: (eds): Rheumatology. 3rd ed.
2. Stein R: Manual of Rheumatology and Outpatient Orthopedic Disorders. London, Philadelphia, Elsevier, 2003, p 233.
Boston, Little, Brown, 1981. 19. Schumacher HR Jr: Synovial fluid analysis, in Katz WA (ed): Diagnosis and
3. Krey PR, Lazaro DM: Analysis of Synovial Fluid. Summit, NJ, CIBA-GEIGY, Management of Rheumatic Diseases. 2nd ed. Philadelphia, JB Lippincott,
1992. 1988, pp 248255.
4. Ropes MW, Bauer W: Synovial Fluid Changes in Joint Disease. Cambridge, 20. Tanphaichitr K, Spilberg I, Hahn B: Lithium heparin crystals simulating cal-
MA, Harvard University Press, 1953. cium pyrophosphate dihydrate crystals in synovial fluid [letter]. Arthritis
5. Hollander JL, Jessar RA, McCarty DJ: Synovianalysis: an aid in arthritis Rheum 9:966, 1976.
diagnosis. Bull Rheum Dis 12:263, 1961. 21. Kerolus G, Clayburne G, Schumacher HR Jr: Is it mandatory to examine syn-
6. Gatter RA, McCarty DJ: Synovianalysis: a rapid clinical diagnostic proce- ovial fluids promptly after arthrocentesis? Arthritis Rheum 32:271, 1989.
dure. Rheumatism 20:2, 1964. 22. Reginato AJ, Schumacher HR Jr: Crystal-associated arthropathies. Clin Geri-
7. Schumacher HR: Synovial fluid analysis. Orthop Rev 13:85, 1984. atr Med 4(2):295, 1988.
8. Greenwald RA: Oxygen radicals, inflammation, and arthritis: pathophysio- 23. Paul H, Reginato AJ, Schumacher HR: Alizarin red S staining as a screening
logical considerations and implications for treatment. Semin Arthritis Rheum test to detect calcium compounds in synovial fluid. Arthritis Rheum 26:191,
20:219, 1991. 1983.
9. Robinson DR, Tashjian AH, Levine L: Prostaglandin E2 induced bone re- 24. Hoffman G, Schumacher HR, Paul H, et al: Calcium oxalate microcrys-
sorption by rheumatoid synovia: a model for bone destruction in RA. J Clin talline associated arthritis in end stage renal disease. Ann Intern Med 97:36,
Invest 56:1181, 1975. 1982.
10. Gray RG, Tenenbaum J, Gottlieb NL: Local corticosteroid injection treat- 25. Reginato AJ, Feweiro JL, Barbazan AC, et al: Arthropathy and cutaneous
ment in rheumatic disorders. Semin Arthritis Rheum 10:231, 1981. calcinosis in hemodialysis oxalosis. Arthritis Rheum 29:1387, 1986.
11. Polley HF, Hunder GG: Rheumatologic Interviewing and Physical Exami- 26. Schumacher HR, Reginato AJ, Pullman S: Synovial fluid oxalate depo-
nation of the Joints. 2nd ed. Philadelphia, WB Saunders, 1978. sition complicating rheumatoid arthritis with amyloidosis and renal fail-
12. Doherty M, Hazelman BL, Hutton CW, et al: Rheumatology Examination ure. Demonstration of intracellular oxalate crystals. J Rheumatol 14:361,
and Injection Techniques. London, WB Saunders, 1992. 1987.
13. Moder KG, Hunder GG: History and physical examination of the muscu- 27. Dornan TL, Blundell JW, Morgan AG: Widespread crystallization of para-
loskeletal system, in Harris ED Jr, Budd RC, Firestein GS, et al: (eds): Kelleys protein in myelomatosis. QJM 57:659, 1985.
Textbook of Rheumatology. 7th ed. Philadelphia, Elsevier Saunders, 2005, 28. Shmerling RH: Synovial fluid analysis. A critical reappraisal. Rheum Dis
p 483. Clin North Am 20(2):503, 1994.
14. McCarty DJ Jr: A basic guide to arthrocentesis. Hosp Med 4:77, 1968. 29. Mahowald ML: Gonococcal arthritis, in Hochberg MC, Silman AJ, Smolen
15. Gottlieb NL, Riskin WG: Complications of local corticosteroid injections. JS, et al: (eds): Rheumatology. 3rd ed. London, Mosby, 2003, p 1067.
JAMA 243:1547, 1980. 30. Shmerling RH, Delbanco TL, Tosteson ANA, et al: Synovial fluid tests. What
16. Hollander JL: Intrasynovial steroid injections, in Hollander JL, McCarty DL should be ordered? JAMA 264:1009, 1990.
Jr (eds): Arthritis and Allied Conditions. 8th ed. Philadelphia, Lea & Febiger, 31. Swan A, Amer H, Dieppe P: The value of synovial fluid assays in the di-
1972, p 517. agnosis of joint disease: a literature survey. Ann Rheum Dis 61(6):493,
17. Wise C: Arthrocentesis and injection of joints and soft tissues, in Harris ED 2002.
Jr, Budd RC, Firestein GS, et al: (eds): Kelleys Textbook of Rheumatology. 32. Lakhanpal S, Li CY, Gertz MA, et al: Synovial fluid analysis for diagnosis of
7th ed. Philadelphia, Elsevier Saunders, 2005, p 692. amyloid arthropathy. Arthritis Rheum 30(4):419, 1987.

CHAPTER 20 ANESTHESIA FOR BEDSIDE


PROCEDURES
MARK DERSHWITZ

When a patient in an intensive care unit (ICU) requires a bed- COMMON PAIN MANAGEMENT
side procedure, it is usually the attending intensivist, as opposed
to a consultant anesthesiologist, who directs the administration
PROBLEMS IN ICU PATIENTS
of the necessary hypnotic, analgesic, and/or paralytic drugs.
Furthermore, unlike in the operating room, the ICU usually Dosing of Agent
has no equipment for the administration of gaseous (e.g., ni-
trous oxide) or volatile (e.g., isoflurane) anesthetics. Anesthesia Selecting the proper dose of an analgesic to administer is prob-
for bedside procedures in the ICU is thus accomplished via a lematic for several reasons, including difficulty in assessing the
technique involving total intravenous anesthesia (TIVA). effectiveness of pain relief, pharmacokinetic (PK) differences
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Chapter 20: Anesthesia for Bedside Procedures 161

between the critically ill and other patients, and normal physi- 80 Propofol
ologic changes associated with aging. Midazolam
70 Sufentanil
Remifentani

Context-Sensitive
Assessing the Effectiveness of Pain Relief 60

Half-Time (min)
Critically ill patients are often incapable of communicating 50
their feelings because of delirium, obtundation, or endotracheal 40
intubation. This makes psychologic evaluation quite difficult 30
because surrogate markers of pain intensity (e.g., tachycardia,
20
hypertension, and diaphoresis) are inherent in the host response
to critical illness. 10
0
Pharmacokinetic Considerations 0 100 200 300 400 500 600
Infusion Duration (min)
Most of the pressors and vasodilators administered in the
ICU by continuous intravenous (IV) infusion have a relatively FIGURE 20.2. The context-sensitive half-times for propofol [4], mida-
straightforward PK behavior: they are water-soluble molecules zolam [5], sufentanil [6], and remifentanil [7] as a function of infusion
that are bound very little to plasma proteins. In contrast, the duration.
hypnotics and opioids used in TIVA have high lipid solubility
and most are extensively bound to plasma proteins, causing
their PK behavior to be far more complex. Figure 20.1 shows
the disappearance curves of fentanyl and nitroprusside after sensitive half-times (CSHTs). This concept may be defined as
bolus injection. The fentanyl curve has three phases: (i) a very follows: when a drug is given as an IV bolus followed by an
rapid phase (with a half-life of 0.82 minutes) lasting about IV infusion designed to maintain a constant plasma drug con-
10 minutes, during which the plasma concentration decreases centration, the time required for the plasma concentration to
more than 90% from its peak value; (ii) an intermediate phase fall by 50% after termination of the infusion is the CSHT [3].
(with a half-life of 17 minutes) lasting from about 10 min- Figure 20.2 depicts the CSHT curves for the medications most
utes to an hour; and (iii) finally a terminal, very slow phase likely to be used for TIVA in ICU patients.
(with a half-life of 465 minutes) beginning about an hour after PK behavior in critically ill patients is unlike that in normal
bolus injection. After a single bolus injection of fentanyl, the subjects for several reasons. Because ICU patients frequently
terminal phase occurs at plasma concentrations below which have renal and/or hepatic dysfunction, drug excretion is signifi-
there is a pharmacologic effect. However, after multiple bolus cantly impaired. Hypoalbuminemia, common in critical illness,
injections or a continuous infusion, this latter phase occurs at decreases protein binding and increases free drug concentration
therapeutic plasma concentrations. Thus, fentanyl behaves as [8]. Because free drug is the only moiety available to tissue re-
a short-acting drug after a single bolus injection, but as a very ceptors, decreased protein binding increases the pharmacologic
long-lasting drug after a continuous infusion of more than an effect for a given plasma concentration. It is therefore more im-
hour in duration (i.e., fentanyl accumulates). Thus, it is inap- portant in ICU patients that the doses of medications used for
propriate to speak of the half-life of fentanyl. TIVA are individualized for a particular patient.
The disappearance curve of nitroprusside has two phases: (i)
a very rapid phase (with a half-life of 0.89 minute) lasting about
10 minutes, during which the plasma concentration decreases Physiologic Changes Associated with Aging
more than 85% from its peak value, and (ii) a terminal phase People 65 years of age and older comprise the fastest grow-
(with a half-life of 14 minutes). It may be slightly slower in ing segment of the population and constitute the majority of
offset as compared with fentanyl during the initial 10 minutes patients in many ICUs. Aging leads to (a) a decrease in total
after a bolus injection, but it does not accumulate at all even body water and lean body mass; (b) an increase in body fat
after a prolonged infusion. and, hence, an increase in the volume of distribution of lipid-
The PK behavior of the lipid-soluble hypnotics and anal- soluble drugs; and (c) a decrease in drug clearance rates, due
gesics given by infusion may be described by their context- to reductions in liver mass, hepatic enzyme activity, liver blood
flow, and renal excretory function. There is a progressive, age-
dependent increase in pain relief and electroencephalographic
100 suppression among elderly patients receiving the same dose of
opioid as younger patients. There is also an increase in central
% of Maximum concentration

Fentanyl
nervous system (CNS) depression in elderly patients following
Nitroprusside
administration of identical doses of benzodiazepines.
10

1
Selection of Agent
Procedures performed in ICUs today (Table 20.1) span a spec-
trum that extends from those associated with mild discom-
0.1 fort (e.g., esophagogastroscopy) to those that are quite painful
0 30 60 90 120 150 180 210 240 (e.g., orthopedic manipulations, wound debridement, and tra-
Time (min) cheostomy). Depending on their technical difficulty, these pro-
cedures can last from minutes to hours. To provide a proper
FIGURE 20.1. The time courses, on a semilogarithmic scale, of the
plasma concentrations of fentanyl [1] and nitroprusside [2] following anesthetic, medications should be selected according to the na-
a bolus injection. Each concentration is expressed as the percentage of ture of the procedure and titrated according to the patients re-
the peak plasma concentration. The fentanyl curve has three phases sponse to surgical stimulus. In addition, specific disease states
with half-lives of 0.82, 17, and 465 minutes. The nitroprusside curve should be considered in order to maximize safety and effective-
has two phases with half-lives of 0.89 and 14 minutes. ness.
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162 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 2 0 . 1 invasive procedures to reduce plasma catecholamine and stress


hormone levels.
BEDSIDE PROCEDURES AND ASSOCIATED LEVELS OF
DISCOMFORT Renal and/or Hepatic Failure
Mildly to moderately uncomfortable Risk of an adverse drug reaction is at least three times higher in
Transesophageal echocardiographya patients with azotemia than in those with normal renal func-
Transtracheal aspiration tion. This risk is magnified by excessive unbound drug or drug
Thoracentesisa metabolite(s) in the circulation and changes in the target tis-
Paracentesisa sue(s) induced by the uremic state.
Liver failure alters many drug volumes of distribution by im-
Moderately to severely uncomfortable pairing synthesis of the two major plasma-binding proteins: al-
Endotracheal intubationa bumin and 1 -acid glycoprotein. In addition, reductions in hep-
Flexible bronchoscopya atic blood flow and hepatic enzymatic activity decrease drug
Thoracostomya clearance rates.
Bone marrow biopsy
Colonoscopy
Peritoneal dialysis catheter insertiona
Peritoneal lavagea
CHARACTERISTICS OF SPECIFIC
Percutaneous gastrostomya AGENTS USED FOR BEDSIDE
Percutaneous intra-aortic balloon insertiona PROCEDURES
Extremely painful
Rigid bronchoscopy
Debridement of open wounds
Hypnotics
Dressing changes The characteristics of the hypnotics are provided in Table 20.2,
Orthopedic manipulations whereas their recommended doses are provided in Table 20.3.
Tracheostomya When rapid awakening is desired, propofol and etomidate are
Pericardiocentesis/pericardial windowa the hypnotic agents of choice. Ketamine may be useful when
Open lung biopsy a longer duration of anesthesia is needed. Midazolam is rarely
Ventriculostomya used alone as a hypnotic; however, its profound anxiolytic and
a amnestic effects render it useful in combination with other
Procedures in which the level of discomfort may be significantly
mitigated by the use of local anesthesia. agents.

Propofol
Description. Propofol is a hypnotic agent associated with
Head Trauma pleasant emergence and little hangover. It has essentially
replaced thiopental for induction of anesthesia, especially in
Head-injured patients require a technique that provides effec- outpatients. It is extremely popular because it is readily titrat-
tive, yet brief, anesthesia so that the capacity to assess neuro- able and has more rapid onset and offset kinetics than midazo-
logic status is not lost for extended periods of time. In addi- lam. Thus, patients emerge from anesthesia more rapidly after
tion, the technique must not adversely affect cerebral perfusion propofol than after midazolam, a factor that may make propo-
pressure. If the effects of the anesthetics dissipate too rapidly, fol the preferred agent for sedation and hypnosis in general and
episodes of agitation and increased intracranial pressure (ICP) for patients with altered level of consciousness in particular.
may occur that jeopardize cerebral perfusion. In contrast, if the The CSHT for propofol is about 10 minutes following a
medications last too long, there may be difficulty in making an 1-hour infusion, and the CSHT increases about 5 minutes for
adequate neurologic assessment following the procedure. each additional hour of infusion for the first several hours, as
shown in Figure 20.2. Thus, the CSHT is about 20 minutes
after a 3-hour infusion. The CSHT rises much more slowly
Coronary Artery Disease
for infusions longer than a day; a patient who is sedated (but
Postoperative myocardial ischemia following cardiac and non- not rendered unconscious) with propofol for 2 weeks recovers
cardiac surgery strongly predicts adverse outcome [9]. Accord- in approximately 3 hours [10]. This rapid recovery of neuro-
ingly, sufficient analgesia should be provided during and after logic status makes propofol a good sedative in ICU patients,

TA B L E 2 0 . 2
CHARACTERISTICS OF INTRAVENOUS HYPNOTIC AGENTSa

Propofol Etomidate Ketamine Midazolam Fospropofol

Onset Fast Fast Fast Intermediate Intermediate


Duration Short Short Intermediate Intermediate Short
Cardiovascular effects None Minimal
Respiratory effects Minimal
Analgesia None None Profound None None
Amnesia Mild Mild Profound Profound Mild
a
The listed doses should be reduced 50% in elderly patients. Entries in bold type indicate noteworthy differences among the drugs.
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Chapter 20: Anesthesia for Bedside Procedures 163

TA B L E 2 0 . 3
USUAL DOSES OF INTRAVENOUS ANESTHETIC AGENTS GIVEN BY CONTINUOUS INFUSIONa

Propofol Etomidate Ketamine Midazolam Sufentanil Remifentanil

Bolus dose (mg/kg) 12 0.20.3 12 0.050.15 0.51.5 0.51.5


Infusion rate (g/kg/min) 100200 NRb 25100 0.251.5 0.010.03 0.050.5
a
The usual doses are for patients without preexisting tolerance and significant cardiovascular disease. The required doses will be higher in patients
with tolerance, and should be reduced in elderly patients and in patients with decreased cardiovascular function. In all cases, the medications should be
titrated to specific endpoints as described in the text.
b
Not recommended due to the possibility of prolonged adrenal suppression.

especially those with head trauma, who may not tolerate me- Currently available propofol preparations contain ethylenedi-
chanical ventilation without pharmacologic sedation. aminetetraacetic acid (EDTA), metabisulfite, or benzyl alcohol
Even though recovery following termination of a con- as a bacteriostatic agent. Because EDTA chelates trace metals,
tinuous infusion is faster with propofol than with midazo- particularly zinc, serum zinc levels should be measured daily
lam, a comparative trial showed that the two drugs were during continuous propofol infusions. Hyperlipidemia may oc-
roughly equivalent in effectiveness for overnight sedation of cur, particularly in infants and small children. Accordingly,
ICU patients [11]. For long-term sedation (e.g., more than triglyceride levels should be monitored daily in this popula-
1 day), however, recovery is significantly faster in patients given tion whenever propofol is administered continuously for more
propofol. than 24 hours.
In spontaneously breathing patients sedated with propo-
fol, respiratory rate appears to be a more predictable sign of Fospropofol
adequate sedation than hemodynamic changes. The ventila-
tory response to rebreathing carbon dioxide during a main- Fospropofol is a water-soluble prodrug of propofol. Fospropo-
tenance propofol infusion is similar to that induced by other fol is metabolized to propofol by the action of alkaline phos-
sedative drugs (i.e., propofol significantly decreases the slope phatase. The peak hypnotic effect occurs in about 10 minutes
of the carbon dioxide response curve). Nevertheless, sponta- following a bolus injection. The kinetic disposition of liberated
neously breathing patients anesthetized with propofol are able propofol differs from that of injected propofol emulsion, with
to maintain normal end-tidal carbon dioxide values during the former being slower for reasons that are as yet unexplained
minor surgical procedures. [16,17]. Apparent advantages of an aqueous solution of fos-
Bolus doses of propofol in the range of 1 to 2 mg per kg propofol are the reduced risk of bacterial contamination as
induce loss of consciousness within 30 seconds. Maintenance compared to propofol emulsion and the absence of a lipid load
infusion rates of 100 to 200 g per kg per minute are adequate that has been associated with organ toxicity during long-term
in younger subjects to maintain general anesthesia, whereas infusions of propofol emulsion. Although fospropofol does not
doses should be reduced by 20% to 50% in elderly individuals. usually cause pain at the site of injection, it commonly causes
a burning sensation distant to the site of injection, typically in
the perineum or buttocks. Although it is currently approved
Adverse Effects
for procedural sedation only, it may find utility for sedation or
Cardiovascular. Propofol depresses ventricular systolic func-
anesthesia in the ICU.
tion and lowers afterload, but has no effect on diastolic func-
Because the molecular weight of fospropofol is higher than
tion [12,13]. Vasodilation results from calcium channel block-
that of propofol, its administered dose is necessarily higher.
ade. In patients undergoing coronary artery bypass surgery,
The package label is unfortunately written in terms of dosing
propofol (2 mg per kg IV bolus) produced a 23% fall in mean
in volume units; because virtually every other medication used
arterial blood pressure, a 20% increase in heart rate, and a
in the ICU is dosed in terms of an infusion rate that is a function
26% decrease in stroke volume. In pigs, propofol caused a
of the body mass, such doses will be used here. The marketed
dose-related depression of sinus node and His-Purkinje system
preparation contains 3.5% fospropofol (35 mg per mL). The
functions, but had no effect on atrioventricular node function
manufacturer recommends a bolus dose of 6.5 mg per kg fol-
or on the conduction properties of atrial and ventricular tissues.
lowed by repeat injections of 1.6 mg per kg no more often than
In patients with coronary artery disease, propofol administra-
every 4 minutes; an infusion rate of 400 g per kg per minute
tion may be associated with a reduction in coronary perfusion
following the bolus dose would be equivalent. Furthermore,
pressure and increased myocardial lactate production [14].
the manufacturer recommends that the doses be decreased by
25% in persons older than 65 years or with severe systemic
Neurologic. Propofol may improve neurologic outcome and
disease. These dose recommendations are designed to achieve
reduce neuronal damage by depressing cerebral metabolism.
procedural sedation and not general anesthesia. As with propo-
Propofol decreases cerebral oxygen consumption, cerebral
fol, the dose will likely need to be increased two- to threefold
blood flow, and cerebral glucose utilization in humans and an-
to induce and maintain general anesthesia; however, no such
imals to the same degree as that reported for thiopental and
study in human beings has yet been published.
etomidate [15]. Propofol frequently causes pain when injected
into a peripheral vein. Injection pain is less likely if the injection
site is located proximally on the arm or if the injection is made
Etomidate
via a central venous catheter. Description. Etomidate has onset and offset PK characteris-
tics similar to propofol and an unrivaled cardiovascular pro-
Metabolic. The emulsion used as the vehicle for propofol con- file, even in the setting of cardiomyopathy [18]. Not only does
tains soybean oil and lecithin and supports bacterial growth; etomidate lack significant effects on myocardial contractility,
iatrogenic contamination leading to septic shock is possible. but baseline sympathetic output and baroreflex regulation of
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164 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

sympathetic activity are well preserved. Etomidate depresses in Because pulmonary hypertension is a characteristic feature
a dose-related manner cerebral oxygen metabolism and blood of acute respiratory distress syndrome (ARDS), drugs that in-
flow without changing the intracranial volumepressure rela- crease right ventricular afterload should be avoided. In infants
tionship. with either normal or elevated pulmonary vascular resistance,
Etomidate is particularly useful (rather than thiopental or ketamine does not affect pulmonary vascular resistance as long
propofol) in certain patient subsets: patients with hypovolemia, as constant ventilation is maintained, a finding also confirmed
those with multiple trauma with closed-head injury, and those in adults.
with low ejection fraction, severe aortic stenosis, left main coro- Cerebral blood flow does not change when ketamine is in-
nary artery disease, or severe cerebral vascular disease. Etomi- jected into cerebral vessels. In mechanically ventilated pigs with
date may be contraindicated in patients with established or artificially produced intracranial hypertension in which ICP
evolving septic shock because of its inhibition of cortisol syn- is on the shoulder of the compliance curve, 0.5 to 2.0 mg
thesis (see later). per kg IV ketamine does not raise ICP; likewise, in mechan-
ically ventilated preterm infants, 2 mg per kg IV ketamine does
not increase anterior fontanelle pressure, an indirect monitor
Adverse Effects of ICP [31,32]. Unlike propofol and etomidate however, ke-
Metabolic. Etomidate, when given by prolonged infusion, may tamine does not lower cerebral metabolic rate. It is relatively
increase mortality associated with low plasma cortisol levels contraindicated in patients with an intracranial mass, with in-
[19]. Even single doses of etomidate can produce adrenal cor- creased ICP, or who have suffered recent head trauma.
tical suppression lasting 24 hours or more in normal patients
undergoing elective surgery [20]. These effects are more pro-
nounced as the dose is increased or if continuous infusions Adverse Effects
are used for sedation. Etomidate-induced adrenocortical sup- Psychologic. Emergence phenomena following ketamine anes-
pression occurs because the drug blocks the 11-hydroxylase thesia have been described as floating sensations, vivid dreams
that catalyzes the final step in the synthesis of cortisol. It is (pleasant or unpleasant), hallucinations, and delirium. These
also noteworthy that etomidate causes the highest incidence of effects are more common in patients older than 16 years, in
postoperative nausea and vomiting of any of the IV anesthetic females, after short operative procedures, after large doses
agents. (>2 mg per kg IV), and after rapid administration (>40 mg per
In 2005, Jackson warned against the use of etomidate in pa- minute). Pre- or concurrent treatment with benzodiazepines or
tients with septic shock [21]. Since then, there have been several propofol usually minimizes or prevents these phenomena [33].
studies that have attempted to confirm or refute the safety of
etomidate in critically ill patients, including those with sepsis.
Cardiovascular. Because ketamine increases myocardial oxy-
Unfortunately, some of these studies purportedly confirmed the
gen consumption, there is risk of precipitating myocardial is-
danger of etomidate [2225], whereas others support its con-
chemia in patients with coronary artery disease if ketamine is
tinued use in patients with sepsis [2630].
used alone. On the other hand, combinations of ketamine plus
diazepam, ketamine plus midazolam, or ketamine plus sufen-
Ketamine tanil are well tolerated for induction in patients undergoing
coronary artery bypass surgery. Repeated bolus doses are often
Description. Ketamine induces a state of sedation, amnesia, associated with tachycardia. This can be reduced by adminis-
and marked analgesia in which the patient experiences a strong tering ketamine as a constant infusion.
feeling of dissociation from the environment. It is unique Ketamine produces myocardial depression in the isolated
among the hypnotics in that it reliably induces unconscious- animal heart. Hypotension has been reported following ke-
ness by the intramuscular route. Ketamine is rapidly metabo- tamine administration in hemodynamically compromised pa-
lized by the liver to norketamine, which is pharmacologically tients with chronic catecholamine depletion.
active. Ketamine is both slower in onset and offset as compared
with propofol or etomidate following IV infusion.
Many clinicians consider ketamine to be the analgesic of Neurologic. Ketamine does not lower the minimal elec-
choice in patients with a history of bronchospasm. In the usual troshock seizure threshold in mice. When administered with
dosage, it decreases airway resistance, probably by blocking aminophylline, however, a clinically apparent reduction in
norepinephrine uptake, which in turn stimulates -adrenergic seizure threshold is observed.
receptors in the lungs. In contrast to many -agonist bron-
chodilators, ketamine is not arrhythmogenic when given to
patients with asthma receiving aminophylline.
Midazolam
Ketamine may be safer than other hypnotics or opioids in Description. Although capable of inducing unconsciousness in
unintubated patients because it depresses airway reflexes and high doses, midazolam is more commonly used as a sedative.
respiratory drive to a lesser degree. It may be particularly use- Along with its sedating effects, midazolam produces anxiolysis,
ful for procedures near the airway, where physical access and amnesia, and relaxation of skeletal muscle.
ability to secure an airway are limited (e.g., gunshot wounds Anterograde amnesia following midazolam (5 mg IV) peaks
to the face). Because ketamine increases salivary and tracheo- 2 to 5 minutes after IV injection and lasts 20 to 40 minutes. Be-
bronchial secretions, an anticholinergic (e.g., 0.2 mg glycopy- cause midazolam is highly (95%) protein bound (to albumin),
rrolate) should be given prior to its administration. In patients drug effect is likely to be exaggerated in ICU patients. Recov-
with borderline hypoxemia despite maximal therapy, ketamine ery from midazolam is prolonged in obese and elderly patients
may be the drug of choice because it does not inhibit hypoxic and following continuous infusion because it accumulates to
pulmonary vasoconstriction. a significant degree. In patients with renal failure, active con-
Another major feature that distinguishes ketamine from jugated metabolites of midazolam may accumulate and delay
most other IV anesthetics is that it stimulates the cardiovas- recovery. Although flumazenil may be used to reverse excessive
cular system (i.e., raises heart rate and blood pressure). This sedation or respiratory depression from midazolam, its dura-
action appears to result from both direct stimulation of the tion of action is only 15 to 20 minutes. In addition, flumazenil
CNS with increased sympathetic nervous system outflow and may precipitate acute anxiety reactions or seizures, particularly
blockade of norepinephrine reuptake in adrenergic nerves. in patients receiving chronic benzodiazepine therapy.
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Chapter 20: Anesthesia for Bedside Procedures 165

Midazolam causes dose-dependent reductions in cerebral large intestines), often leading to adynamic ileus, appear to be
metabolic rate and cerebral blood flow, suggesting that it may mediated both peripherally (by opioid receptors located in the
be beneficial in patients with cerebral ischemia. gut) and centrally (by the vagus nerve).
Because of its combined sedative, anxiolytic, and amnestic
properties, midazolam is ideally suited for both brief, relatively Cardiovascular. Hypotension is not unusual following mor-
painless procedures (e.g., endoscopy) and prolonged sedation phine administration, especially if it is given rapidly (i.e., 5
(e.g., during mechanical ventilation). to 10 mg per minute). In patients pretreated with both H1 -
and H2 -antagonists, the hypotensive response following mor-
Adverse Effects phine administration is significantly attenuated, despite compa-
Respiratory. Midazolam (0.15 mg per kg IV) depresses the rable increases in plasma histamine concentrations. These data
slope of the carbon dioxide response curve and increases the strongly implicate histamine as the mediator of these changes.
dead spacetidal volume ratio and arterial PCO2 . Respiratory
depression is even more marked and prolonged in patients with
chronic obstructive pulmonary disease (COPD). Midazolam Respiratory. Morphine administration is followed by a dose-
also blunts the ventilatory response to hypoxia. dependent reduction in responsiveness of brain stem respi-
ratory centers to carbon dioxide. Key features of this phe-
Cardiovascular. Small (<10%) increases in heart rate and nomenon include a reduction in the slope of the ventilatory
small decreases in systemic vascular resistance are frequently and occlusion pressure responses to carbon dioxide, a right-
observed after administration of midazolam. It has no signifi- ward shift of the minute ventilatory response to hypercarbia,
cant effects on coronary vascular resistance or autoregulation. and an increase in resting end-tidal carbon dioxide and the ap-
neic threshold (i.e., the PCO2 value below which spontaneous
Neurologic. Because recovery of cognitive and psychomotor ventilation is not initiated without hypoxemia). The duration
function may be delayed for up to 24 hours, midazolam as the of these effects often exceeds the time course of analgesia. In
sole hypnotic may not be appropriate in situations where rapid addition to blunting the carbon dioxide response, morphine
return of consciousness and psychomotor function are a high decreases hypoxic ventilatory drive. Morphine administration
priority. in patients with renal failure has been associated with pro-
longed respiratory depression secondary to persistence of its
active metabolite, morphine-6-glucuronide [35].
The administration of small doses of IV naloxone (40 g) to
Opioids patients in order to reverse the ventilatory depressant effect of
morphine may produce some adverse effects. Anecdotal reports
Morphine describe the precipitation of vomiting, delirium, arrhythmias,
Description. Pain relief by morphine and its surrogates is rel- pulmonary edema, cardiac arrest, and sudden death subsequent
atively selective in that other sensory modalities (touch, vibra- to naloxone administration in otherwise healthy patients after
tion, vision, and hearing) are not obtunded. Opioids blunt pain surgery. Furthermore, the duration of action of naloxone is
by (i) inhibiting pain processing by the dorsal horn of the spinal shorter than any of the opioids it may be used to antagonize
cord, (ii) decreasing transmission of pain by activating descend- (except remifentanil). Recurring ventilatory depression there-
ing inhibitory pathways in the brain stem, and (iii) altering the fore remains a distinct possibility, and in the spontaneously
emotional response to pain by actions on the limbic cortex. breathing patient, it is a source of potential morbidity.
Various types of opioid receptors (denoted by Greek let- Reversal with a mixed opioid agonistantagonist agent such
ters) have been discovered in the CNS. The classical pharma- as nalbuphine or butorphanol appears to be safer than with
cologic effects of morphine such as analgesia and ventilatory naloxone. Mixed opioid agonistantagonist agents may either
depression are mediated by -receptors. Other -effects in- increase or decrease the opioid effect, depending on the dose
clude sedation, euphoria, tolerance and physical dependence, administered, the particular agonist already present, and the
decreased gastrointestinal motility, biliary spasm, and miosis. amount of agonist remaining.
The -receptor shares a number of effects with the -receptor, For bedside procedures in the ICU, many of these problems
including analgesia, sedation, and ventilatory depression. The can be obviated by using a shorter acting opioid.
-receptor is responsible for mediating some of the analgesic ef-
fects of the endogenous opioid peptides, especially in the spinal Neurologic. Morphine has little effect on cerebral metabolic
cord. Few of the clinically used opioids have significant activity rate or cerebral blood flow when ventilation is controlled. Mor-
at -receptors at the usual analgesic doses. phine may affect cerebral perfusion pressure adversely by low-
Morphine is a substrate for the P-glycoprotein, a protein ering mean arterial pressure.
responsible for the transport of many molecules out of cells.
The combination of slow CNS penetration due to lower lipid
solubility and rapid efflux accounts for the slow onset of mor-
Fentanyl and Its Congeners
phines CNS effects. Peak analgesic effects may not occur for Description. Fentanyl, sufentanil, and remifentanil enter and
more than an hour after IV injection; hence, the plasma profile leave the CNS much more rapidly than does morphine, thereby
of morphine does not parallel its clinical effects [34]. causing a much faster onset of effect after IV administration.
Morphine is unique among the opioids in causing signif- The only significant difference among these agents is their PK
icant histamine release after IV injection that occurs almost behavior.
immediately. The beneficial effect of giving morphine to a pa- Fentanyl may be useful when given by intermittent bolus in-
tient with acute pulmonary edema is far more related to this jection (50 to 100 g), but when given by infusion, its duration
hemodynamic effect rather than to its analgesic and sedating becomes prolonged [36]. For TIVA in ICU patients in whom
effects. rapid emergence is desirable, sufentanil or remifentanil is the
preferred choice for continuous infusion. When the procedure
Adverse Effects is expected to be followed by postoperative pain, sufentanil is
Gastrointestinal. Constipation, nausea, and/or vomiting are preferred. Figure 20.2 shows that its CSHT is similar to that
well-described side effects of morphine administration. Re- of propofol for infusions of up to 10 hours. When the proce-
duced gastric emptying and bowel motility (both small and dure is expected to be followed by minimal postoperative pain
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166 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

(e.g., bronchoscopy), remifentanil is preferred. Its CSHT is


about 4 minutes regardless of the duration of the infusion. PRACTICAL CONSIDERATIONS
Remifentanil owes its extremely short duration to rapid FOR TIVA
metabolism by tissue esterases, primarily in skeletal muscle
[37]. Its PK behavior is unchanged in the presence of severe Electing to perform common procedures (e.g., tracheostomy
hepatic [38] or renal [39] failure. and percutaneous gastrostomy) in the ICU instead of the oper-
Sufentanil infusion for TIVA may be initiated with a 0.5 to ating room represents a potential cost saving of tremendous
1.5 g per kg bolus followed by an infusion at 0.01 to 0.03 scope. Not only does this strategy eradicate costly operat-
g per kg per minute. If given with a propofol infusion, the ing room time and support resources, it eliminates misadven-
two infusions may be stopped simultaneously as governed by tures that sometimes occur in hallways and on elevators. Cost
the curves in Figure 20.2. Remifentanil infusion for TIVA may analyses estimate an average overall cost reduction of 50%
be initiated with a 0.5 to 1.5 g per kg bolus followed by an or more compared with traditional operative procedures [40].
infusion at 0.05 to 0.5 g per kg per minute. The remifentanil TIVA represents the most cost-effective method of facilitating
infusion should be continued until after the procedure is com- this.
pleted; if the patient is expected to have postoperative pain, In most patients, safe and effective TIVA may be achieved
another opioid should be given because the remifentanil effect via the infusions of propofol plus sufentanil or propofol plus
will dissipate within a few minutes. remifentanil. Premedication with midazolam decreases the re-
quired propofol doses and decreases the likelihood of recall for
Adverse Effects intraoperative events. Bolus doses should not be used in hemo-
Cardiovascular. Although fentanyl, sufentanil, and remifen- dynamically unstable patients, and lower bolus doses should
tanil do not affect plasma histamine concentrations, bolus be used in elderly individuals. NMB agents are also given if
doses can be associated with hypotension, especially when needed.
infused rapidly (i.e., <1 minute). This action is related to The opioid infusion rate is titrated to minimize signs of in-
medullary vasomotor center depression and vagal nucleus stim- adequate analgesia (e.g., tachycardia, tachypnea, hypertension,
ulation. sweating, and mydriasis), although differentiation of pain from
the sympathetic responses to critical illness is difficult. The
propofol infusion rate is titrated to the endpoint of loss of
Neurologic. Fentanyl and sufentanil have been reported to in- consciousness; the depth of anesthesia monitors that are based
crease ICP in ventilated patients following head trauma. They on analysis of the electroencephalogram waveform (bispectral
may adversely affect cerebral perfusion pressure by lowering index (BIS), patient state index (PSI), or spectral entropy) fa-
mean arterial pressure. All of the fentanyl derivatives may cause cilitate locating this endpoint more accurately. Loss of con-
chest wall rigidity when a large bolus is given rapidly. This effect sciousness should be achieved prior to the initiation of muscle
may be mitigated by neuromuscular blocking (NMB) agents as paralysis. It is possible for patients to be completely aware of
well as by coadministration of a hypnotic agent. intraoperative events at times when there is no change in hemo-
dynamics or any manifestation of increased sympathetic activ-
ity [41,42]. Hence, administering an opioid to blunt incisional
pain without inducing loss of consciousness with a hypnotic is
NEUROMUSCULAR inappropriate.
BLOCKING AGENTS The following additional points deserve consideration in
this context:
There are two pharmacologic classes of NMB agents (see
Chapter 25): depolarizing agents (e.g., succinylcholine) and 1. In subhypnotic doses, propofol is less effective than midazo-
nondepolarizing agents (e.g., vecuronium and cisatracurium). lam in producing amnesia. In the absence of coadministra-
Succinylcholine is an agonist at the nicotinic acetylcholine re- tion of a benzodiazepine, propofol must cause unconscious-
ceptor of the neuromuscular junction. Administration of suc- ness in order to reliably prevent recall. Prompt treatment of
cinylcholine causes an initial intense stimulation of skeletal patient responses (movement, tachycardia, and hyperten-
muscle, manifested as fasciculations, followed by paralysis due sion) is important.
to continuing depolarization. Nondepolarizing agents are com- 2. Medications infused for TIVA should be given via a carrier
petitive antagonists of acetylcholine at the neuromuscular junc- IV fluid running continuously at a rate of at least 50 mL
tion; they prevent acetylcholine, released in response to motor per hour. This method not only helps deliver medication
nerve impulses, from binding to its receptor and initiating mus- into the circulation, but also serves as another monitor of
cle contraction. Distinctions among the nondepolarizing agents occlusion of the drug delivery system. Occlusion of the in-
are made on the basis of PK differences as well as by their fusion line for more than a few minutes may lead to patient
cardiovascular effects. awareness.
NMB agents are used to facilitate endotracheal intubation 3. To take advantage of the known CSHT values for the TIVA
and improve surgical conditions by decreasing skeletal muscle agents, communication with the surgeon during the proce-
tone. Prior to intubation, the administration of an NMB agent dure is important in order to anticipate the optimum time
results in paralysis of the vocal cords, increasing the ease with for stopping the infusions. The sufentanil and propofol in-
which the endotracheal tube may be inserted and decreasing fusions are stopped in advance of the end of the procedure,
the risk of vocal cord trauma. During surgery, the decrease in whereas remifentanil is infused until the procedure is com-
skeletal muscle tone may aid in surgical exposure (as during plete.
abdominal surgery), decrease the insufflation pressure needed 4. To maintain reasonably constant propofol and sufentanil
during laparoscopic procedures, and make joint manipulation blood concentrations, the maintenance infusion rates should
easier during orthopedic surgery. NMB agents should not be be decreased during the procedure because the plasma con-
used to prevent patient movement, which is indicative of inad- centrations increase over time at constant infusion rates. An
equate anesthesia. Dosing of NMB agents should be based on approximate guideline is a 10% reduction in infusion rate
monitoring evoked twitch response; ablation of two to three every 30 minutes.
twitches of the train-of-four is sufficient for the majority of 5. Strict aseptic technique is important especially during the
surgical procedures and permits easy reversal. handling of propofol.
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Chapter 20: Anesthesia for Bedside Procedures 167

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by computer-controlled infusion pump. Anesthesiology 73:1091, 1990. insufficiency in patients with septic shock after the administration of etomi-
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Anaesth 64:704, 1990. 23. Cotton BA, Guillamondegui OD, Fleming SB, et al: Increased risk of adrenal
3. Hughes MA, Glass PS, Jacobs JR: Context-sensitive half-time in multicom- insufficiency following etomidate exposure in critically injured patients. Arch
partment pharmacokinetic models for intravenous anesthetic drugs. Anes- Surg 143:62, 2008.
thesiology 76:334, 1992. 24. Tekwani KL, Watts HF, Chan CW, et al: The effect of single-bolus etomidate
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70:426, 1989. 27. de Jong MF, Beishuizen A, Spijkstra JJ, et al: Predicting a low cortisol re-
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17. Struys MM, Vanluchene AL, Gibiansky E, et al: Aquavan r injection, a 38. Dershwitz M, Hoke JF, Rosow CE, et al: Pharmacokinetics and pharma-
water-soluble prodrug of propofol, as a bolus injection: a phase I dose- codynamics of remifentanil in volunteer subjects with severe liver disease.
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18. Goading JM, Wang JT, Smith RA, et al: Cardiovascular and pulmonary re- dynamics of remifentanil in subjects with renal failure compared to healthy
sponses following etomidate induction of anesthesia in patients with demon- volunteers. Anesthesiology 87:533, 1997.
strated cardiac disease. Anesth Analg 58:40, 1979. 40. Barba CA, Angood PB, Kauder DR, et al: Bronchoscopic guidance makes
19. Ledingham IM, Finlay WEI, Watt I, et al: Etomidate and adrenocortical percutaneous tracheostomy a safe, cost effective, and easy to teach proce-
function. Lancet 1:1434, 1983. dure. Surgery 118:879, 1995.
20. Fragen RJ, Shanks CA, Molteni A, et al: Effects of etomidate on hormonal 41. Ausems ME, Hug CC Jr, Stanski DR, et al: Plasma concentrations of alfen-
responses to surgical stress. Anesthesiology 61:652, 1984. tanil required to supplement nitrous oxide anesthesia for general surgery.
21. Jackson WJ: Should we use etomidate as an induction agent for endotra- Anesthesiology 65:362, 1986.
cheal intubation in patients with septic shock? A critical appraisal. Chest 42. Philbin DM, Rosow CE, Schneider RC, et al: Fentanyl and sufentanil anes-
127:1031, 2005. thesia revisited: How much is enough? Anesthesiology 73:5, 1990.
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168 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

CHAPTER 21 INTERVENTIONAL
ULTRASOUND
GISELA I. BANAUCH AND PAUL H. MAYO

technique. Intuitively, ultrasound guidance is an attractive


INTRODUCTION alternative to traditional technique. It is now in widespread
use in the critical care community. This chapter reviews the use
Ultrasonography has major applications in critical care of ultrasonography for the guidance of a variety of procedures
medicine. When used at the bedside by the intensivist who is that are commonly performed by the intensivist.
in charge of the clinical management of the case, it allows for
immediate diagnosis and management decisions to be made
at the point of care. Bedside, intensivist-performed ultrasound GENERAL PRINCIPLES
differs substantially from standard radiology or cardiology per-
formed ultrasonography in that the intensivist acquires the im- 1. To maximize the utility of ultrasonography, the operator
age, interprets the image, and promptly applies the results to should have basic knowledge of ultrasound physics, ma-
the clinical situation. This avoids the time delay and clinical chine control, transducer manipulation, image acquisition,
disassociation implicit to ultrasonography that is performed ultrasound anatomy, image orientation, and image interpre-
on a consultative basis by radiology or cardiology services. tation. In addition, the intensivist must have full capability
The scope of practice of critical care ultrasonography en- in all the mechanical aspects of the procedure.
compasses those aspects of the discipline that have utility to 2. The machine should be carefully positioned such that the op-
diagnosis and management of the critically ill patient. A sum- erator may view the screen and the procedure site without
mary of the important elements that are required for compe- untoward head movement; this often requires rearrange-
tence in the field have been presented in a recent consensus ment of cluttered equipment that typically surrounds the
statement [1]. Ultrasonography may be divided into two gen- patient bed in the critical care unit. Machine position for er-
eral categories of application in critical care management: (i) gonomic efficiency is particularly important when using ul-
to guide diagnosis and management and (ii) for purposes of trasonography for real-time image-guided needle insertion.
procedural guidance. The two are often related. For example, Room lighting and angle of the ultrasound machines screen
ultrasonography may be used to diagnose a pleural effusion. should be adjusted to minimize screen glare. Before starting
Ultrasonography is then used to guide thoracentesis, which in the procedure, machine settings should be set for optimal
turn is useful in identifying the cause of the pleural effusion image quality with attention to gain, depth, and image ori-
and therefore its management. This chapter reviews the use of entation. Many modern machines are designed such that
ultrasonography for procedural guidance in the intensive care the structure of interest is best visualized if it is placed in the
unit (ICU). For detailed review of critical care ultrasonogra- center of the screen. Some machines have automated image
phy, the reader is referred to comprehensive texts on the subject optimization software so that the operator does not need
[2,3]. to adjust controls beyond pushing a single control button.
A major responsibility of the intensivist is to safely per- The resulting image may not, in fact, be optimal, and it may
form a wide variety of invasive procedures that may be as- need further readjustment.
sociated with significant complications. The proceduralist has 3. In situations where real-time guidance is required (e.g., vas-
a specific target, such as a vascular structure or body com- cular access) or when there is need for scanning while main-
partment (e.g., pleural, peritoneal, or pericardial), and seeks taining a sterile field, ultrasound procedure guidance re-
to avoid injury to adjacent structures while assuring accurate quires that the operator use a purpose-designed sterile probe
placement of the needle. Inaccurate placement of the needle cover. The use of covers made from sterile gloves or sterile
may injure adjacent structures with potential major morbidity intravenous skin covers is strongly discouraged. They fre-
or even life-threatening complication, as well as lead to failure quently fail during the procedure, while the operators at-
of either diagnostic effort or essential vascular or body cavity tention is focused on the sonographic image or on needle
access. direction and insertion on the sterile field. Well-designed
This discussion assumes that the reader is fully trained in sterile transducer covers are low cost and come with sterile
physical tasks of the procedure (proper sterile technique, needle ultrasound coupling medium.
manipulation, wire insertion, dilation etc.). These are reviewed 4. By standard convention, guidance of thoracic, abdominal,
in other chapters of this text specific to each procedure. Ultra- and vascular procedures requires that the screen orienta-
sonography is used to augment the safety and success rate of tion marker be placed on the left of the screen. Guidance of
the operator who is fully competent in the mechanical aspects procedures related to the heart, such as pericardiocentesis
of the procedure. or transvenous pacemaker insertion, is performed with the
The use of ultrasonography for procedural guidance is based screen orientation marker placed on the right of the screen.
on a simple principle. The safety and success of needle insertion This convention relates purely to common usage patterns.
is augmented by the ability to image the target; to identify and When scanning from the head of the patient, as with in-
therefore avoid adjacent structures; and if required, to guide ternal jugular venous (IJV) access, the operator needs to
real-time needle insertion. The alternative is to rely on off-line decide on how to orient the screen marker in reference to
analysis of standard radiography images and/or on landmark the transducer. We suggest that the orientation marker be
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Chapter 21: Interventional Ultrasound 169

on the left of the screen and that the corresponding marker manikins of excellent design are now commercially available
on the transducer always be held such that it is pointed to- [11]. Trainees may practice ultrasound control of the needle
ward the left side of the examiner (unless scanning the vessel and targeted vascular access multiple times before their first
in longitudinal axis when the transducer marker is directed effort at the patient bedside. This is imperative for patient
cephalad). It is important to understand and standardize safety and comfort as well as for operator confidence.
orientation and transducer marker position so that the op-
erator can direct the needle in predictable fashion during
real-time guidance of needle insertion. Ultrasound Guidance of Vascular Access
5. Whenever planning an ultrasound-guided procedure, the
operator should explore the structure of interest before Vascular access is a major responsibility of the intensivist. In-
prepping and draping the patient. This allows for optimal sertion of catheters of varying size and function requires central
site selection before site preparation. If the procedure aims venous cannulation, accurate ongoing measurement of arterial
to cannulate a vessel (e.g., central venous or arterial catheter- pressure and waveform requires arterial line insertion, whereas
ization), the potential target should be evaluated on both peripheral venous (PV) access is a routine requirement of pa-
sides of the body unless absolute contraindications exist on tient care. Considerations such as obesity or unusual body habi-
one side (e.g., arteriovenous fistula in the upper extremity tus (e.g., kyphoscoliosis or genetic disease) and coagulopathy
would preclude radial arterial catheterization on that side). may present special challenges. PV access may be difficult in
Multiple studies have documented significant anatomic vari- patients due to obesity, intravenous drug use, or chemother-
ability in vascular lumina, positioning, and location with apy. Ultrasound is uniquely useful for guidance of all forms of
respect to adjacent structures for both venous and arterial vascular access.
targets [49]. A benefit of ultrasound guidance of vascular access is that
6. Initially, vascular structures should be imaged in their trans- it allows the operator to identify contraindications to vascu-
verse axis, as this approach is best to differentiate the artery lar access that are not apparent by simple physical examina-
and the vein [10]. Features such as compressibility, pul- tion. For example, marked respiratory effort may completely
sation, luminal variation with respiratory effort, and/or obliterate internal jugular and subclavian vein lumina during
respiratory maneuvers can all be used to help distinguish inspiration in the volume-depleted patient. Such intermittent
arterial from venous vessels. The cross-sectional ultrasono- luminal collapse precludes successful vascular access and can-
graphic view usually displays the vein in close proximity not be identified, except with ultrasonography. The presence
to its accompanying artery, thus facilitating comparison of of a thrombus in the femoral vein (FV) frequently cannot be
vessel changes with dynamic maneuvers, such as compres- detected by physical examination, but it is readily identified ul-
sion and Valsalva. Detection of vessel pulsatility requires a trasonographically and contraindicates cannulation at that site.
steady imaging plane for at least a few seconds. Pulsatility Ultrasonography thus warns the operator to redirect attention
is sometimes diminished with hypotension. Differentiation to less complication-prone sites.
of arterial from venous structures is challenging especially
when the patients perfusion is maintained with a nonpul-
satile ventricular assist device (impeller device). The much
less compressible, thicker arterial walls, as well as the lack SPECIFIC PROCEDURES
of vessel lumen variability with respiratory effort and/or res-
piratory maneuvers, provide the most reliable features that Internal Jugular Venous Access
differentiate arterial from venous structures in this situation.
Color and spectral Doppler analysis may occasionally be re- Several studies report that ultrasound guidance of IJV access
quired to distinguish the vein from the artery in situations is superior to landmark technique, with lower complication
of difficult anatomy or in the subclavian position. and higher success rate [12]. The reasons for this are obvious.
7. For pleural or abdominal access, initial orientation should Landmark technique may be straightforward in a slender sub-
always be achieved in the longitudinal image plane. The ject, but much less so in an obese subject. Asymmetric IJV size
variable position of the diaphragm in the critically ill patient and variation in IJV position relative to the carotid occur in up
makes is easiest to differentiate intrathoracic from intra- to 30% of the normal population and cannot be appreciated by
abdominal fluid collections using longitudinal image planes. surface physical examination [13,14]. A national quality orga-
8. Whenever possible, the operator should document relevant nization has stated that ultrasound guidance of IJV access is re-
ultrasound images during the procedure. This may be as quired for patient safety purposes [15]. The Residency Review
simple as capturing a frozen video image that can be placed Committee has stated that training in this technique is highly
in the chart. Depending on system capability, video clips recommended during critical care fellowship training; this will
may be captured and stored off line. Image documentation is likely be followed by it becoming a mandatory requirement.
important for quality review and billing purposes. However, In guiding IJV access, ultrasonography should be used in a
it may not be practical in all situations, particularly during methodical fashion in order to maximize its utility as follows:
hectic resuscitation efforts.
9. Ultrasound guidance of procedures requires specific train- 1. Vascular access requires the use of a linear ultrasound
ing. The cognitive aspects of the field are straightforward, transducer typically of 7.5 MHz frequency. This allows
and can be easily learned from books, audiovisual sources, for adequate resolution of structures that are relatively
courses, or via e-learning program. Image interpretation and near the surface of the body. Lower frequency transduc-
acquisition require a component of hands-on scanning un- ers, which penetrate more deeply at the cost of reduced
der the supervision of a skilled bedside instructor. Real-time resolution, are not suitable for guidance of vascular access.
guidance of needle insertion is a complex psychomotor skill The patient should be placed in Trendelenburg in order to
that requires practice. Unfortunately, this is often achieved distend the vein as much as possible.
with the experiential approach; that is, the inexperienced 2. The operator should perform a preliminary scan of both
operator is expected to perform the procedure the first time sides of the neck before the sterile preparation. This al-
on an actual patient. To avoid this, we strongly recom- lows for identification of aberrant anatomy and/or throm-
mend that training in real-time needle insertion take place on bus, and determination of the best site, angle, and depth of
an ultrasound manikin. Ultrasound-capable vascular access needle penetration. The IJV is usually lateral to the carotid
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170 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

artery when scanning the anterior neck, and is differenti- is advantageous. A variation of ultrasound guidance of
ated from the carotid artery by its larger size, thin wall, and vascular access is the mark-and-stick technique wherein
lack of characteristic pulsation, easy compressibility, size the operator identifies the vessel and marks an appropriate
fluctuation with respiration or respiratory maneuvers, and site for line insertion. The needle is introduced without the
the presence of thin mobile venous valves. Color Doppler benefit of real-time guidance. Although this yields higher
may be used to confirm, but it is not generally required. success rate than traditional landmark method, it is inferior
The examination of the vein starts with a two-dimensional to real-time guidance [12] and so is not discussed further.
(2-D) study to examine the anatomy and observe for visi- 6. The operator needs to decide whether to use transverse
ble echogenic thrombus. The 2-D examination is followed or longitudinal scanning plane for real-time needle guid-
by compression of the vessel to exclude isoechoic throm- ance. This is based on personal preference and training
bus not visible on 2-D imaging. A fully compressible IJV background. Some skilled operators prefer longitudinal
indicates that there is no thrombus at the site of the exam- approach, as they maintain that it is easier to identify the
ination. In order to ensure patency of the vessel along the needle in long axis and therefore to guide it into the vessel.
length that will be traversed by the central venous catheter, Many operators prefer the transverse plane. In either case,
several sites along the course of the vessel must be exam- maximal safety is achieved by maintaining clear identifica-
ined and then compressed. The presence of an ipsilateral tion of the needle tip throughout the procedure [17].
thrombus contraindicates line insertion, whereas the pres- 7. There are two general approaches to real-time guidance in
ence of a contralateral thrombus is of concern, as the pro- the transverse scanning plane. The first, which is concep-
posed IJV insertion may itself predispose to thrombus. This tually easier, is to insert the needle very close to the trans-
may yield bilateral IJV thrombus, which is undesirable. ducer and angle down toward the vessel, with the goal of
3. The preprocedure scan should include examination of the identifying the needle tip as it enters the scanning plane
anterior lung (with the patient in supine position) in or- and the vessel. This technique results in a very acute angle
der to rule out pneumothorax before the procedure. The at which the vessel is accessed, which sometimes makes it
transducer is held perpendicular to the chest wall in order difficult to thread the guidewire. Alternatively, the needle
to examine the rib interspaces of the upper anterior chest. may be introduced at some distance from the target ves-
The pleural interface is identified between the rib shad- sel. The transducer is then moved toward the needle until
ows. Presence of lung sliding, lung pulse, or B-lines rules the needle tip is identified. The transducer and needle tip
out pneumothorax with a high level of certainty [16]. The are then moved forward in tandem, with the needle tip
examination may be accomplished with similar result, us- adjusted at the appropriate angle. In this manner, visual
ing a low-frequency abdominal or cardiac transducer, or control of the needle tip is maintained throughout its for-
using a high-frequency vascular transducer that is used to ward movement. In addition, the angle at which the vessel
guide vascular access. Following the procedure, the oper- is accessed tends to be less acute, making it easier to thread
ator again examines the anterior chest for pneumothorax. the guidewire. With the longitudinal scanning method, the
The finding of pneumothorax following the procedure, transducer is used to obtain a longitudinal image of the tar-
when none existed before, is strong evidence for procedu- get vessel. The needle is introduced along the longitudinal
ral mishap. The preprocedure chest examination should midline of the transducer and kept in full view while it is
include both lungs to cover the very rare eventuality that moved toward the vessel wall. The longitudinal approach
the patient has a contralateral pneumothorax before the tends to result in the least acute angle at which the vessel
procedure. is accessed, making it easiest to thread the guidewire into
4. Before the sterile field is established, the ultrasound ma- the vessel successfully even when the vessel is located rela-
chine must be positioned to allow optimal handeye coor- tively far from the skin surface, for example, in the obese
dination for the operator. Because the operator normally patient.
stands on the side of the IJV to be cannulated, next to 8. A vexing problem with IJV access is vessel compression.
the patients head and facing the patients feet, the optimal Under ultrasound guidance, the advancing needle may
position for the ultrasound machine is on the operators compress the anterior wall of the IJV, often to the ex-
side of the patient, immediately adjacent to the patients tent that the vascular lumen is effaced. With further for-
lower chest or upper abdomen. Inadequate placement of ward movement of the needle, it passes through the poste-
the ultrasound screen makes efficient handeye coordina- rior wall of the vessel. Frequently, as the needle is slowly
tion very difficult. With an inappropriately placed ultra- withdrawn, the vessel lumen opens up, blood enters the
sound screen, the operator needs to rotate his or her head needle and syringe, and the wire is passed without prob-
in order to compare changes in the ultrasound image with lem. Whether minor needle insertion through the posterior
changes in needle insertion depth and angle. With a well- wall has any clinical implication or not has not been deter-
placed ultrasound screen, the operator needs to only move mined. It may be avoided by downward orientation of the
his or her head up or down in order to compare ultrasono- bevel and careful attention to angulation of the needle, as
graphic image changes with changes in needle angle and well as positioning the patient in Trendelenburg. Extensive
insertion depth on the sterile field. The chance of acciden- head rotation or head extension and the presence of a la-
tally changing the ultrasonographic imaging plane (thus ryngeal mask airway all reduce IJV diameter and move the
losing the ultrasound image essential for real-time guid- vein into a position anterior to the carotid artery, thus in-
ance) during head rotation is much greater than the chance creasing the risk of inadvertent arterial puncture [1820].
of an inadvertent change in scanning plane during a simple 9. Following wire insertion and before dilation of the ves-
up-and-down movement of the head. sel, the location of the wire in a venous vessel should be
5. Following preliminary scanning and appropriate place- documented. This is best achieved in a longitudinal view
ment of the ultrasound unit, the patient is prepared with of the vessel. If the wire is found to be in the artery (an
standard sterile technique. The transducer is covered with occasional event, particularly with a less experienced op-
a purpose-designed sterile transducer cover. The operator erator), it may be removed without great consequence to
has a choice at this point. A helper may hold the transducer the patient. However, inadvertent dilation of the carotid
while the operator introduces the needle, or the operator artery may have catastrophic effect. Positive identification
may hold the transducer in one hand while guiding the nee- of the wire within the vein adds only a short additional
dle with the other. The latter is the preferred technique. The time to the procedure and avoids a rare, but dangerous,
ability to manipulate the transducer and needle in tandem complication.
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Chapter 21: Interventional Ultrasound 171

10. Generally, a postprocedure chest radiograph is used to doc- ultrasound guidance of SCV access presents a psychologic
ument proper position of the venous catheter. Ultrasonog- challenge. The operator is so used to relying on the clavicle
raphy may be used as an alternative method [21]. Identi- as a definitive structural guide during insertion that it is dif-
fication of suboptimal line position with ultrasonography ficult to perform the access at a lateral site that ignores the
allows repositioning while the sterile field is still in place, clavicle landmark completely. More lateral puncture sites,
unlike a delayed chest radiograph. However, identification however, are anatomically less risky for both arterial and
of line position with ultrasonography adds several minutes pleural puncture, whereas vessel lumen is reduced only by
to the procedure and requires a high level of ultrasound 25% [25].
training. 4. Because the puncture site of the subclavian vein is consid-
11. Following the procedure, the operator should examine the erably more lateral for ultrasound-guided punctures com-
anterior chest in order to rule out procedure-related pneu- pared to landmark-guided punctures, the tip of the central
mothorax. The presence of sliding lung, lung pulse, and/or venous catheter may not reach to the superior vena cava
B-lines excludes pneumothorax. This underlines the im- when a short catheter is used. This is especially true when
portance of performing ultrasonography both before and the left subclavian vein is used for access.
after the procedure. The loss of lung sliding, lung pulse, 5. For safety purposes, the operator should use the same
and/or B-lines following IJV central venous access, when precautions as with the IJV insertion by checking for
they were present immediately before the procedure, is pneumothorax before and after the procedure and by doc-
strong evidence for a procedure-related pneumothorax. Ul- umenting that the wire is within the vein before dilation.
trasonography is more accurate than standard supine chest Unlike the IJV and FV, where wire identification is straight-
radiography for the detection of pneumothorax, and has forward, identification of the wire in the subclavian vein
similar accuracy as chest computerized tomography [22]. may be difficult, as the clavicle may block easy identifica-
tion. A useful technique is to image the ipsilateral IJV and
follow it down to the medial supraclavicular area. Down-
ward rotation of the probe reveals the confluence of the IJV
Subclavian Venous Access and the SCV with wire identification.
Ultrasonography may be used to guide SCV access [23,24].
The authors opinion is that ultrasound guidance of SCV ac-
cess may not augment safety or success in patients with normal Femoral Venous Access
anatomy. However, it does have utility in patients with chal-
lenging anatomy or coagulopathy. It also requires a higher skill Ultrasonography may be used to guide FV access [26], and has
level than IJV or FV access. It should only be used by the op- the same rationale as for the IJV. It reduces complication rate
erator who has a high level of competence in real-time needle and improves success rate. It has particular utility in emergency
guidance. The pleural surface is in close proximity to the SCV situations that mandate immediate venous access. A trained
and so accurate identification and precise control of the needle operator can safely establish venous access very rapidly using
tip are required in order to avoid a pneumothorax. Many of the ultrasound guidance. Many of the principles described for IJV
principles described for IJV insertion apply to the SCV. What insertion apply to the FV site. What follows are concerns that
follows are concerns that are specific to this site: are specific to this site:
1. The SCV is more difficult to locate than the IJV. One strategy 1. The safe site for FV access should be at the common femoral
is to scan the upper chest with the transducer in longitudi- vein (CVF) level. Immediately below the inguinal crease,
nal scanning plane in order to locate the clavicle. Once this the FV rotates so that it is posterior to the artery (then be-
is done, the transducer is moved laterally along the clavicle coming the superficial FV). Attempts at access at this level
until the vessel is seen to appear from under the clavicle. risk arterial injury. In the worst-case scenario, the needle
Further lateral movement of the transducer will image the passes through the artery into the vein. Following dilation,
SCV independent of the clavicle. At this point, the trans- the catheter is passed through the artery and rests, as a fully
ducer is rotated 90 degrees to obtain a long axis view of the functional venous line, in the vein. Subsequently, it is re-
vein. This is the appropriate orientation for real-time guid- moved with no special precaution as the operator believes
ance of needle insertion. The subclavian artery is located that it was a well-placed venous line. Major arterial bleeding
immediately adjacent to the vein, and most often deep to ensues. Ultrasonography allows identification of the CFV
it. Unfortunately, the vein may not be compressible due to in a position that is medial to the vein at a site close to
anatomic constraint, so it may be challenging to differenti- the inguinal ligament. This is the appropriate site for needle
ate the artery from the vein. Observation of respirophasic puncture. The position of the vein remains side by side with
changes, venous valves, and the use of color and pulse wave the artery for a longer distance caudally if the leg is rotated
Doppler all have utility in making the critical distinction externally (similar to optimal positioning for insertion using
between the two structures. It is difficult to visualize SCV the landmark technique [27]).
thrombus, as compression study is often not possible. Lack 2. Identification of the vein and artery is straightforward and is
of respirophasic changes and/or lack of color Doppler flow based on methods outlined in the discussion on IJV access.
augmentation on compression of the ipsilateral arm suggest The vessel should be imaged in transverse plane and the
the possibility of thrombus. needle guided into it under real-time ultrasound control. The
2. In order to minimize operator head movement during the wire should be documented within the vein before dilation.
insertion, the ultrasound machine should be positioned im-
mediately adjacent to the patients axilla on the side that is
contralateral to the side at which access will be attempted
(e.g., adjacent to the patients right axilla if the left SCV has
Peripheral Venous Access
been chosen for venous access). Ultrasound guidance for PV access improves success rates
3. Ultrasound guidance of SCV access should be performed and reduces complications [28]. Site-specific considerations for
with the vein imaged in its long axis so that the entire needle ultrasound-guided PV insertion follow:
and its tip can be visualized real time throughout the inser-
tion. Any loss of needle tip control runs the risk of pleural or 1. The operator must have knowledge of the complex venous
arterial puncture. For the experienced landmark operator, anatomy of the upper extremity. Accessing PVs may be
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172 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

performed using both cross-sectional and longitudinal scan- ceeding with thoracentesis, operators must be completely
ning techniques. The advantage of the latter is that the nee- confident in their identification of fluid within the thorax.
dle is visualized along its entire length so that it may be 2. It is important that the patient maintain the same position
guided accurately into a small venous structure. between ultrasonographic site localization and actual de-
vice insertion. If the patient changes position between ul-
trasonographic site localization and actual device insertion,
Arterial Access free-flowing fluid may redistribute to a different area in the
hemithorax. A large pleural effusion is easy to locate by
Principles for ultrasound guidance of arterial access are similar scanning in the midaxillary line. It may be more difficult to
to those for ultrasound guidance of venous access. Particular identify a safe access site in patients with smaller effusions,
points of importance for each arterial access site follow. as the mattress blocks appropriate transducer position in
the supine patient. In this situation, the operator may need
to reposition the patient for better access.
Radial Artery 3. When localizing a safe access site and angle, the operator
Ultrasound-guided radial arterial cannulation has been shown should explore its extent in all three dimensions. This re-
to significantly increase success on the first attempt [29], and is quires imaging the collection in two orthogonal planes (typ-
especially valuable in hypotensive and grossly edematous pa- ically, a longitudinal and a coronal plane). A moderate-sized
tients. In the patient without edema, the artery is located quite collection that tracks into an interlobar fissure may appear
superficially at the wrist. Color Doppler imaging can help in to have a considerable extent, with a wide separation be-
its identification. The artery is accompanied by two easily col- tween parietal and visceral pleural surface, if its long axis is
lapsible venous structures, the venae comitantes. Wrist exten- imaged; however, an orthogonal scan in a coronal plane will
sion beyond 60 degrees reduces vessel diameter, thus making quickly reveal the small lateral extent of such a collection.
cannulation more difficult [8]. When determining where to insert the device, the opera-
tor must take into consideration not only the optimal point
Femoral Artery on the thoracic skin, but also the angle with the thorax in
which the ultrasound transducer provides the image of the
Ultrasound guidance for femoral arterial access has been collections largest extent. This optimal transducer angle for
proved valuable in obese and hypotensive patients [30]. The imaging of the collection must then be reproduced without
technique is also of benefit in coagulopathic patients. In ad- continuous ultrasonographic guidance during insertion of
dition, ultrasound allows selection of a vessel site that is less the device. Reproduction of the optimal imaging angle as-
affected by atherosclerotic changes, as well as permits prompt sures that the largest extent of the fluid collection is accessed
detection of complications due to catheterization, such as pseu- during device insertion. In this manner, fluid collections with
doaneurysm, hematoma, or arteriovenous fistula [31,32]. a separation between visceral and parietal pleural surfaces
of 15 mm or more can be accessed safely [34].
4. The hypoechoic space between parietal and visceral pleura
Ultrasound Guidance of Pleural Access is usually presumed to contain fluid; however, gelatinous
contents can occasionally present with a similar ultrasono-
Pleural fluid collections are frequently encountered in critically graphic image [36]. If sterile transducer sheaths are available
ill patients. Ultrasound guidance of thoracentesis reduces the during the procedure, the operator can image the intratho-
risk of pneumothorax [33]. Ultrasound-guided thoracentesis racic device position if no fluid return is achieved, thus assur-
is safe for patients on mechanical ventilatory support [34,35]. ing access to the intended space. If color Doppler signals are
Ultrasound guidance for pleural access and device insertion imaged in the hypoechoic space on preinsertion scanning,
should incorporate the following points: this also assures liquid rather than gelatinous intrathoracic
contents [37].
1. Prior to establishing the sterile field, a comprehensive scan
of the hemithorax should be undertaken with the aim of If a pleural device is inserted in order to perform medical
identifying a safe site, angle, and depth for needle insertion. pleurodesis, the extent of pleurodesis can be assessed in follow-
It is of paramount importance that the operators first ac- up pleural ultrasound 1 to 2 days later and repeat ultrasound-
tion be a differentiation between peritoneal and retroperi- guided local pleurodesis can then be performed in locules with
toneal structures and pleural structures. This requires un- persistent fluid content [38].
equivocal identification of the diaphragm. In the intubated,
sedated patient, the diaphragm is often located more cra-
nially than in the awake, upright patient. The prudent op- Ultrasound Guidance of Pericardiocentesis
erator first proceeds with identification of the kidney and
the adjacent liver or spleen in the longitudinal axis. The Pericardiocentesis may be performed safely with ultrasound
operator then scans more cranially, identifying the curvilin- guidance [39]. The intensivist performs pericardiocentesis for
ear diaphragm with its characteristic respiratory movement. diagnostic purposes. Alternatively, pericardiocentesis may be
Positive identification of the diaphragm avoids inadvertent a lifesaving procedure if the patient has pericardial tampon-
subdiaphragmatic needle insertion with its potentially lethal ade. The skills required for performance of ultrasound-guided
effect. Pleural fluid, unless loculated, assumes a dependent pericardiocentesis are similar to those required for thoracen-
position in the hemithorax. In the supine patient, the fluid tesis and paracentesis. The operator must identify a safe site,
is posterior in location. Ultrasonographically, pleural fluid angle, and depth for needle insertion that avoids injury to struc-
appears as a hypoechoic space that is subtended by typical tures adjacent to the pericardial fluid. This requires that the
anatomic boundaries (inside of chest wall and diaphragm) operator examine the heart from multiple windows: paraster-
and associated with typical dynamic findings (lung flapping, nal, apical, and subcostal. Using ultrasonography, the operator
diaphragmatic movement, plankton sign, and mobile ele- identifies the largest area of fluid collection. This is often at the
ments within the fluid, such as septations). Complex effu- apical four-chamber view, or in large effusions, from a paraster-
sions, such as empyema or hemothorax, may be difficult to nal view. The subcostal approach is frequently prohibited by
identify by the inexperienced ultrasonographer. Before pro- the presence of the liver in a blocking position, a feature that is
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Chapter 21: Interventional Ultrasound 173

easily recognized with ultrasonography. The use of fluoroscopy guided peritoneal access. Specifically, a comprehensive scan of
to guide pericardiocentesis is typically limited to the subcostal the abdomen should first ascertain the area of maximal in-
approach. The liver is not easily identified using fluoroscopy, traperitoneal fluid, and the patient should maintain the same
so hepatic laceration is a hazard that is not readily apparent position between the ultrasonographic site localization and the
when using fluoroscopy. In addition, the apical or parasternal actual procedure so as to avoid fluid redistribution. The oper-
windows frequently reveal a larger fluid collection target than ator should explore the extent of the peritoneal fluid collection
does the subcostal approach. Some concerns specific to peri- using two orthogonal planes. In addition, the operator who ac-
cardiocentesis are as follows: cesses the peritoneal space under ultrasound guidance should
bear in mind the following:
1. Lacerations of the myocardium or a coronary artery are
specific potentially lethal complications of pericardiocente- 1. The best site, angle, and depth for needle penetration are de-
sis. Site selection requires that there be sufficient fluid to termined at the bedside. The needlesyringe assembly must
allow safe needle insertion. In making this determination, duplicate the angle at which the transducer was held when
the operator must observe for cardiac movement that oc- determining the best angle of attack. Normally, an area supe-
curs during contractile cycle, which is respirophasic or re- rior to and medial to the left anterosuperior iliac spine con-
sults from cardiac swinging within the effusion. A minimum tains some of the free intra-abdominal fluid in the left para-
of 10 mm of space within the effusion is required for safe colic gutter (similar to the area identified with the landmark
needle insertion. Large effusions may allow the operator to technique). Because the sigmoid colon courses retroperi-
select an angle of approach that is free of any cardiac struc- toneally at this location, the risk of large bowel injury is
ture. The presence of interposed liver may preclude a sub- less than that on the contralateral side, which contains the
costal approach. Aerated lung does not permit transmission intraperitoneal cecum. Perihepatic and perisplenic fluid col-
of ultrasound so that the ultrasonographic visualization of lections also occur in patients with ascites, but the risk of
the heart precludes injury to interposed aerated lung. Con- solid organ injury is higher in these locations, and the op-
solidated lung has a specific ultrasonographic appearance, erator should have experience prior to attempting puncture
and must not be interposed in the planned needle track. A at these subdiaphragmatic sites.
coexisting pleural effusion may be interposed between the 2. In the edematous patient, compression of the subcutaneous
pericardial effusion and the needle insertion site. The pleu- tissue leads to an underestimation of the soft-tissue dis-
ral effusion should be removed before the pericardial fluid tance that needs to be traversed prior to entering the peri-
is accessed. toneal space (so-called compression artifact). Any ultra-
2. Once the site is selected, it should be marked without placing sonographic measurement of the distance between the skin
traction on the skin that may cause inadvertent site move- and the peritoneal cavity should thus be performed from an
ment on release of the traction. The depth of needle penetra- image acquired while the transducer is applied to the skin
tion is a critical measurement. Compression artifact caused with minimal pressure.
by firm pressure of the transducer in the obese or edema-
tous patient may cause an underestimation of the depth of
needle penetration. This needs to be factored into the depth Other Ultrasound-Guided Procedures
estimate; otherwise the operator will not be able to access
the pericardial fluid, out of mistaken concern that the nee- Beyond vascular access, thoracentesis, paracentesis, and peri-
dle has been inserted too far. Angle selection is determined cardiocentesis, ultrasonography may be used to guide other
by the location of the fluid. Whenever possible, it should be procedures of interest to the intensivist as follows:
perpendicular to the skin surface, as this is the easiest angle 1. Aspiration and biopsy of solid and fluid-filled structures.
to duplicate with the needle and syringe assembly. Ultrasonography allows the intensivist to identify a fluid-
3. Unlike thoracentesis and paracentesis, it is important to in- filled structure such as an abscess [41]. With knowledge
clude the transducer with full sterile cover into the set up of surrounding anatomy, a safe site, angle, and depth of
of the sterile field. The intensivist should be prepared to needle penetration may be identified for access. Similarly,
rescan the target site just before needle insertion in order solid lesions may be accessed for aspiration and biopsy [42].
to document the correct angle for needle insertion, recheck 2. Airway management. Ultrasonography may be used to doc-
depth in case of initial failure due to compression artifact, ument endotracheal tube placement and diagnose inadver-
and check for proper device position immediately following tent main stem bronchial intubation [43]. Ultrasonography
catheter insertion. is useful in performing percutaneous tracheostomy to screen
4. Real-time guidance of needle insertion is not necessary for for dangerous vascular aberrancy and guide tracheal access.
safe performance of pericardiocentesis, similar to thora- 3. Transvenous pacemaker insertion. Ultrasonography may
centesis and paracentesis. A final confirmatory scan is per- be used to guide transvenous pacemaker insertion. The
formed immediately before needle insertion and the needle subcostal window permits visualization of the IVC, right
is placed with free-hand technique duplicating the angle de- atrium, and right ventricle. The pacemaker wire may be
fined by the transducer. Aspiration of fluid is followed by manipulated into position under real-time guidance.
wire insertion and device insertion via Seldinger technique. 4. Lumbar puncture. Ultrasonography may be used to guide
Correct catheter position may be verified by injection of lumbar puncture [44]. This has application in the patients
agitated saline solution. with difficult anatomy.

Ultrasound Guidance of Paracentesis CONCLUSION


Peritoneal fluid collections commonly occur in the critically Ultrasonography is a useful technique in guiding a variety of
ill. Ultrasound guidance improves the safety of peritoneal procedures that are routine to critical care medicine. These in-
access, especially in patients with peritoneal adhesions or clude vascular access, thoracentesis, paracentesis, and pericar-
difficult anatomy (e.g., morbid obesity and massive subcu- diocentesis. Competence in ultrasonographic guidance is a use-
taneous edema [40]). Many of the principles described for ful skill for the intensivist as it improves the safety, comfort,
ultrasound-guided pleural access also apply to ultrasound- and efficiency of these common procedures.
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174 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

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Chapter 22: Interventional Radiology: Percutaneous Drainage Techniques 175

CHAPTER 22 INTERVENTIONAL
RADIOLOGY: PERCUTANEOUS DRAINAGE
TECHNIQUES
BRIAN T. CALLAHAN, SALOMAO FAINTUCH AND FELIPE B. COLLARES

Over the past decade, image-guided percutaneous drainage equipment, and nature of the collection such as size, location,
procedures have become accepted as safe and effective alterna- and presence of septations. Advantages of ultrasound include
tives to surgery for the first-line treatment of symptomatic fluid portability, lack of radiation, low cost, and real-time visualiza-
collections in the body. Image guidance typically provided by tion of needle placement into a collection. Ultrasound can also
sonography or computed tomography (CT) allows for precise be readily combined with fluoroscopic guidance techniques.
localization of fluid collections, improved drainage techniques, Limitations of ultrasound include poor visualization of deep
and faster patient recovery. Rapid imaging localization and per- collections secondary to large body habitus, bone, overlying
cutaneous treatment has played a major role in decreasing the bowel gas, or surgical dressings. CT provides excellent visual-
morbidity and mortality associated with surgical exploration ization of the fluid collection and its relation to vital structures,
[14]. allowing for the safest percutaneous access route to be cho-
sen. For deep collections such as those located in the pelvis or
retroperitoneal space, CT is particularly well suited [6]. There
GENERAL AIMS is typically a shorter learning curve to master CT-guided pro-
cedures, especially given the availability of commercially pro-
The aim of the interventional radiologist is to detect and local- duced skin grids to help aid needle placement. The main lim-
ize symptomatic fluid collections, ascertain if additional imag- itations of CT include radiation exposure, cost, and lack of
ing or laboratory tests are needed, and determine what, if any, real-time visualization of needle placement. The recent advent
intervention is required. Close communication between inter- of CT fluoroscopy allowing the operator to obtain rapid se-
ventional and critical care staff is essential to accomplish these quential images of needle position without having to leave the
goals. Image-guided aspiration or drainage procedures can al- patient is a major step forward for helping to resolve some
leviate symptoms due to mass effect or inflammation, provide of these technical issues [5]. Table 22.2 is a summary of the
fluid samples for laboratory characterization, and cause reduc- advantages and limitations of CT versus sonography [7].
tion in sepsis [5]. A list of fluid collections amenable to image-
guided procedures is provided in Table 22.1.

INDICATIONS
DIAGNOSTIC IMAGING The indications for image-guided drainage and aspiration in-
CT and ultrasound are the two main imaging modalities used clude, but are not limited to, fluid sampling to assess infected
for percutaneous image guidance. Magnetic resonance imaging versus sterile collections, reduction of microorganism burden
(MRI)-guided drainage is available at some academic institu- due to extraction of contaminated material, and relief of pres-
tions, but limited by availability, cost, and paucity of MRI- sure symptoms secondary to excess fluid accumulation. In the
compatible devices. The choice between CT and ultrasound is critically ill patient, catheter drainage may stabilize the pa-
ultimately determined by operator experience, availability of tients condition so that a more definitive surgical procedure
can be performed at a later time [8,9]. Abscess size is an impor-
tant determinant of the need for percutaneous drainage. Many
patients with abscesses smaller than 4 cm in diameter can be
treated conservatively with broad-spectrum antibiotics, hydra-
TA B L E 2 2 . 1 tion, and bowel rest [10]. If a small collection is unresponsive
to initial antibiotic therapy, a drainage procedure should be
FLUID COLLECTIONS SUCCESSFULLY TREATED WITH considered. In patients with abscesses larger than 4 cm, studies
PERCUTANEOUS DRAINAGE have shown that percutaneous catheter placement is beneficial
and less invasive than surgical intervention [10].
Sterile Nonsterile

Ascites
Hematoma Enteric abscess CONTRAINDICATIONS
Lymphocele Lung abscess and empyema
Pancreatic pseudocyst Ruptured appendicitis Contraindications are divided into absolute and relative. Ab-
Postsurgical seroma Pancreatic abscess solute contraindications for percutaneous drainage include
Urinoma Tubo-ovarian abscess absence of a safe access route or uncorrectable coagulopathy.
Multilocular fluid collections Cholecystitis An uncooperative or unwilling patient may also cause termi-
nation of a procedure. Often, the study may be rescheduled
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176 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 2 2 . 2
ADVANTAGES AND LIMITATIONS OF COMPUTED TOMOGRAPHY (CT) AND ULTRASOUND

Advantages Limitations

CT Excellent 2-D and 3-D (with reformatting) spatial resolution Radiation exposure
Images not obscured by overlying structures Lack of real-time image guidance
Procedures take longer
Higher cost
US No radiation required, real time visualization of anatomy Overlying structures (i.e., bowel gas, real-time visualization of
and needle placement bone) may obscure target
Portability allows bedside procedures More difficult to master
Low cost Need cooperative patient

to allow for general anesthesia or deep sedation to be pro- mination of the imaging modality used to characterize the fluid
vided for patient safety. The utmost care should be taken to collection depends on location and operator preference. Once
avoid transgression of major blood vessels, pleura, pancreas, the collection has been localized, the access route is planned.
and spleen. One should also avoid prolonged drainage of sterile The basic tenets of surgical drainage are followed using estab-
collections due to the risk of secondary infection [11]. In pa- lished surgical routes to find the shortest and least invasive path
tients with relative contraindications, procedures may require while avoiding lung, pleura, bowel, and other vital structures.
more planning or additional time, but are usually amenable to Prior to the procedure, the patient should stop all anticoagu-
treatment. For example, a transenteric (small bowel) route may lant medications, given the benefits of the drainage procedure
allow for needle aspiration of a collection previously thought outweigh the risk to the patient from thrombosis. For example,
to be inaccessible [12]. If no direct route is available, the liver, clopidogrel (Plavix), an antiplatelet agent, should be held for 7
kidney, and stomach may be safely transgressed during needle to 10 days before the procedure [19]. For patients receiving vi-
aspiration or catheter placement. Recent advances in technique tamin K antagonists such as Coumadin, guidelines recommend
such as transgluteal, transvaginal, or transrectal sampling pro- bridging anticoagulation with therapeutic dose low-molecular-
vide more options for draining difficult-to-reach collections weight heparin (given subcutaneously) or intravenous unfrac-
[1315]. tionated heparin (given intravenously) [19,20]. The goal is to
maintain the international normalized ratio (INR) less than
1.5. It is believed that anticoagulants can be safely restarted 6
to 8 hours following the procedure. Coagulation parameters
RISKS, BENEFITS, AND should also be obtained within a few days before the proce-
ALTERNATIVES dure and corrected if necessary. In a nonemergent situation,
the prothrombin time (PT) should be less than 15 seconds, the
Overall complications associated with percutaneous drainage partial thromboplastin time less than 35 seconds, platelet count
are reported to be less than 15% [16]. These include damage to greater than 75,000 per mL and INR less than 1.5. In emergent
vital structures, bleeding, and infection among others. Mortal- situations where the PT is elevated, fresh-frozen plasma should
ity (ranging from 1% to 6%) is frequently secondary to sepsis be given. Platelet transfusions can be administered just prior to
or multiorgan failure rather than the drainage procedure itself. the procedure to raise levels to an acceptable value.
Depending on the location and physical properties of an in- The patient should have nothing to eat for 4 to 6 hours
fected or sterile collection, percutaneous drainage is curative prior to the study to reduce the risk of aspiration during mod-
in 75% to 90% of cases [6,16,17]. In approximately 10% of erate sedation. Transient bacteremia associated with percuta-
cases, percutaneous drainage can serve as a temporizing mea- neous drainage of an infected collection may require prophy-
sure allowing surgery to be postponed or performed in a single lactic treatment with antibiotics. Initial coverage should utilize
step [10]. Patients whose drainage collections contain feculent a broad-spectrum antibiotic before more selective therapy can
material or a fistulous communication tend to respond poorly, be deduced from fluid Gram stain and culture. If intravenous
and further surgical intervention may be required. Indications contrast is required to visualize a collection, the patients renal
for surgery also include visceral perforation, peritonitis, un- function (blood urea nitrogen [BUN] and creatinine) should be
controlled sepsis, and lack of improvement or deterioration of evaluated. If elevated (serum creatinine >1.5 mg per dL), the
clinical status following several days of medical treatment [18]. patient may require hydration and pretreatment with sodium
bicarbonate and oral or intravenous N-acetylcysteine (Mu-
comyst) [21]. Low osmolality contrast agents may also be used
PREPROCEDURE PREPARATION to help reduce the risk of contrast-induced nephrotoxicity. In
patients with a history of prior contrast reaction, the inci-
Regardless of the study to be performed, certain basic prin- dent should be discussed to determine if symptoms were truly
cipals apply to all patients about to undergo a drainage pro- an anaphylactic reaction. In the setting of a validated contrast
cedure. After review of the risks, benefits, and alternatives to reaction, the risks and benefits of the study should be weighed
the procedure, informed consent should be obtained from the and discussed with both the patient and the referring physi-
patient or health care proxy. The radiologist should review the cian. If a decision is made to precede with intravenous con-
case with the referring physician to determine if the procedure trast administration, these patients are usually pretreated with
is medically indicated or if other treatment alternatives exist. a combination of a steroid and an antihistamine. Oral contrast
A comprehensive history and physical examination is taken, may be given to patients prior to CT to better delineate bowel
including review of previous and current imaging studies to loops. Reports of unopacified bowel mistaken for an abscess
evaluate fluid collection size, location, and complexity. Deter- collection are not uncommon.
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Chapter 22: Interventional Radiology: Percutaneous Drainage Techniques 177

microorganisms present. Preferred antiseptics include 70% al-


EQUIPMENT cohol, 10% povidoneiodine, or a chlorhexidine-containing
product [24]. Skin preparation should be performed in a way
With the advent of portable, high-resolution ultrasound ma- that preserves skin integrity and prevents injury to the skin.
chines, diagnostic or therapeutic procedures may now be per- Shaving is no longer recommended because it may create breaks
formed at the bedside. Drainage of ascites, pleural effusions, in the skin where bacteria can multiply and grow. The skin prep
and placement of cholecystostomy tubes are just some of pro- should be large enough to allow for extension of the incision or
cedures performed at our institution when the patient is too placement of adjacent drainage sites. Creating and maintain-
unstable to transport. All procedures must be performed un- ing a sterile field by placing sterile surgical drapes around the
der sterile conditions, with patient monitoring and sedation patients incision large enough to prevent inadvertent contam-
performed by a qualified nurse. For most procedures, con- ination is essential.
venient premade sterile kits are available, containing drapes,
skin preparation, lidocaine, blades, sharps containers, and ad-
ditional instruments tailored to the intervention to be per-
formed. A variety of different-size and -configuration needles, PROCEDURES
guidewires, and catheters should be available to the radiologist
during the procedure.
General Considerations
In principle, a unilocular collection with a well-developed cav-
PATIENT CONSENT AND ity wall is best suited for percutaneous drainage. After local-
PREPROCEDURE REVIEW ization of the collection with either CT or ultrasound, the
patient is placed on the imaging table in the optimal po-
After a thorough explanation of the risks, benefits, and alter- sition that affords the shortest and safest approach to the
natives of the procedure, informed consent should be obtained collection being entered. For multiloculated or semisolid collec-
from the patient or a health care proxy [22]. tions, multiple drain placements may be required. If possible,
A careful review of the procedure time-out should be held drains should be inserted into the most dependent portion of
just prior to gaining access to confirm patient identity, site, the collection.
review allergies and to verify the procedure to be performed.

ANESTHESIA AND MONITORING Diagnostic or Therapeutic Aspiration


CT and ultrasound used alone or with fluoroscopic guidance
Most image-guided drainage procedures can be performed with
can be used to localize the collection. After appropriate pa-
local anesthesia alone or in combination with moderate seda-
tient positioning and selection of the skin insertion site, local
tion. Typically, local anesthesia is achieved using subcutaneous
anesthesia with 1% lidocaine is administered and a small in-
infiltration with 1% to 2% lidocaine using a thin 25-gauge nee-
cision made with a no. 11 scalpel. After the skin entrance site
dle. At our institution, we have found that addition of sodium
is widened with a surgical forceps, a 22- or 20-gauge needle
bicarbonate (75 mg per mL mixed in a 1:10 ratio) to lidocaine
can be advanced into the collection under image guidance. For
reduces the pain perception of an intradermal injection [23].
a hematoma or viscous collection, 16- or 18-gauge large-bore
Longer acting agents such as tetracaine gel or bupivacaine (last-
needles can be used [2,25]. Aspiration of fluid confirms posi-
ing 4 to 8 hours) are available for procedures lasting more than
tion, and can be sent for culture, Gram stain, and cytology if
a couple hours. For moderate sedation, the procedure is typ-
needed. Additional laboratory tests can be added such as in the
ically performed using a combination of intravenous fentanyl
case of evaluating fluid for amylase in a peripancreatic collec-
and midazolam (Versed). The interventional radiologist should
tion or creatinine in suspected urinomas. The aspiration needle
be familiar with these drug protocols and their reactions, and
may be left in place to serve as a guide for parallel catheter
conscious sedation certification is recommended. In procedures
placement or a conduit for introduction of a guidewire.
where balloon dilation is performed or if patients are unable
to hold still for long periods of time, general anesthesia may be
required. The patient should be well hydrated, and vital signs
must be continuously monitored during the procedure as well Catheter Selection
as during the patients recovery. It is imperative that the inter-
ventional suite is equipped with basic monitoring equipment, Multiple types of drainage catheters are available on the mar-
including pulse oximetry, blood pressure monitoring devices, ket. These come in different sizes, configurations, and mate-
and electrocardiography. For the infrequent event of cardiopul- rials. Selection of the appropriate catheter is largely governed
monary resuscitation, a defibrillator, backboard, and code cart by the size, location, and physical properties of the collection
supplied with the necessary medications for advanced life sup- to be drained. The two major catheter designs include sump
port should always be available. and nonsump varieties. A sump catheter is well suited for ab-
scess drainage and ranges in size from 8 to 14 French (Fr). The
catheter contains a small lumen that allows ingress of irrigant
STERILE TECHNIQUE or air for drainage and a larger outer lumen designed to prevent
side-hole blockage when the catheter is apposed against an ab-
Regardless of known risk factors, universal precautions against scess cavity wall [26]. Smaller bore nonsump catheters are usu-
contact exposure should be applied to all patients, including ally more flexible than sump catheters allowing for guidewire
wearing of sterile gloves, impermeable gowns, and a face mask placement into difficult-to-reach fluid collections. Limitations
with shield. Hands should be washed with an antibacterial sur- of nonsump catheters include smaller side holes and internal
gical scrub before starting the procedure. All equipment should bores, limiting their effectiveness in draining viscous collec-
be placed on a sterile field within easy reach, such as a bed- tions, such as pus or hematoma. The largest caliber catheter
side table. Proper preparation of the patients skin using an that can be safely and comfortably inserted should be used to
antimicrobial product is essential in reducing the number of help drain viscous fluid and prevent blockage from debris.
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178 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

easily be lost in inexperienced hands. If this occurs, cavity de-


Therapeutic Catheter Drainage compression may make guidewire reentry nearly impossible. It
is recommended not to evacuate the cavity before the catheter
Broadly, catheter drainage systems can be introduced using the has been secured in position.
trocar or Seldinger technique. The trocar system consists of
an 8- to 16-Fr pigtail catheter coaxially loaded over a hollow
metal stiffener with a sharp inner stylet. Under image guidance, Fixing the Catheter
the trocar system is advanced together into the fluid collection.
Once the catheter has reached the desired location, the inner A wide variety of catheters containing various types of self-
stylet is removed and aspiration performed confirming position locking detention devices are available on the market. The most
within the collection. Next, the catheter is advanced off the frequently used self-locking mechanism consists of a string that
cannula into the cavity, assuming its pigtail configuration. Most when pulled, forms a pigtail at the catheters internal end. The
CT drainages are performed using this system. Advantages of string can then be locked in position fixing the pigtail in place
the trocar technique include a single pass and less chance of to prevent accidental dislodgement. A second type of locking
access loss. The trocar technique is well suited to large, easily device, a Malecot or mushroom catheter can be deployed
accessible collections, and can be performed quickly and safely when the abscess cavity does not contain enough room for pig-
at the bedside under ultrasound guidance. Given the rigidity of tail formation. For drainage, the catheter should be connected
the system, the trocar system is not recommended for drainage to a bag with intervening stopcock to allow for irrigation. Fur-
procedures where the collection is small or difficult to access. ther security can be achieved by fixing the catheter to the skin
An alternative to the trocar system for drain placement is with tape and sutures or a commercially available external fix-
the use of the Seldinger technique (Fig. 22.1). The Seldinger ation device. We have found adhesive external devices to be
system involves two steps starting with insertion of an 18- to particularly well suited to catheter fixation without the need
20-gauge sheathed needle into a collection under image guid- for additional skin suturing.
ance. Following aspiration of fluid to confirm position, the nee-
dle is removed and a 0.035-in. guidewire is advanced through
the sheath into the cavity [27]. The guidewire is subsequently Management of the Catheter
used for tract dilatation and placement of 8- to 12-Fr drainage
catheters. This technique is best performed under continuous The patient with a percutaneous drainage catheter requires reg-
image guidance such a fluoroscopy as guidewire access can ular monitoring. A team approach requiring communication

A B

FIGURE 22.1. A 65-year-old male with development of lymphocele


in left pelvis following radical prostatectomy. A: Computed tomog-
raphy (CT) scan obtained in supine position with overlying skin grid
(arrow) allowing for precise localization of the collection (asterisk) for
percutaneous needle placement. B: CT scan obtained after satisfac-
tory localization with the tip of the needle (dark streak) in the center
C of the collection. C: CT scan obtained after satisfactory placement of
a drainage catheter with a Seldinger technique.
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Chapter 22: Interventional Radiology: Percutaneous Drainage Techniques 179

* *
A B

C D

FIGURE 22.2. A 63-year-old female status postrecent sigmoid resection presenting with abdominal pain.
A: Chest x-ray showing large amount of free intraperitoneal air (asterisks) concerning for bowel perfora-
tion. B: Computed tomography (CT) scan obtained with oral contrast shows large gas and fluid containing
collection (arrow) from leak at the surgical anastomosis. C: CT scan performed after satisfactory position
of drainage catheter into the collection. D: Due to high drainage output (>50 cc per day), abscessogram
was performed demonstrating a fistulous communication (arrow) with the descending colon.

between interventional and critical care staff is critical to pre- instructed in catheter care and to how to recognize any poten-
vent catheter malfunction. Daily rounds should be conducted tial or existing malfunction. The patient is advised to return to
to ensure the catheter is draining and not kinked or dislodged. the department in the event of abdominal pain, leakage from
During rounds, the skin insertion site, catheter tubing, amount the catheter entry site, fever, or chills. When long-term drainage
of drainage, and body temperature should be evaluated. It is is anticipated, catheters should be exchanged approximately
useful to mark the level of the skin insertion on the catheter dur- every 3 months to avoid blockage from encrustation or debris.
ing initial placement to allow for easy assessment of catheter
dislodgement. Most catheters are connected to a bag for ex-
ternal drainage, allowing for evaluation of fluid volume and Patient Response
consistency. Gentle irrigation of the abscess cavity with 10 to
20 mL of sterile saline is recommended three to four times daily Following complete evacuation of purulent material from an
to ensure patency. Vigorous irrigation is not recommended as infected cavity, improved clinical response should be seen in a
expansion of the abscess cavity may lead to transient bac- matter of hours to several days [8,12]. Parameters of improv-
teremia [28]. Dressing changes should also be performed daily. ing clinical status include defervescence, reduction in pain, and
In anticipation of the patients discharge from the hospital, fam- resolution of leukocytosis. If there is no improvement after
ily members are instructed in catheter care or a visiting nursing 2 to 3 days, suspicion should be raised for an undrained col-
service is arranged. The patient and his or her family should be lection, catheter malfunction, or fistula formation. In such
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180 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

cases, follow-up imaging using CT, ultrasound, or fluoroscopy


with contrast injection into the collection is recommended. Ab- Clinical Outcome and Complications
scesses containing loculations are more difficult to drain than
are unilocular collections. Several techniques have been em- Depending on the location and makeup of an infected or sterile
ployed to treat multiloculated collections including placement collection, image-guided percutaneous drainage is successful in
of additional drains or use of guidewires or fibrinolytic agents 70% to 90% of cases. Overall complications are reported to be
(such as urokinase) to break up septations [29]. Semisolid col- less than 15% [14], but most are minor. Major complications
lections such as necrotic tumors, infected hematomas, or pan- (5% to 7% complication rate) include infection, bleeding, sep-
creatic abscesses are also more resistant to drainage and may ticemia, injury to adjacent structures such as bowel and death.
require surgical debridement. Inadvertent contamination of a previously sterile collection is
also a possibility with prolonged catheter drainage [11]. En-
teric transgression can usually be treated conservatively with
delayed catheter removal to allow for a mature fistulous tract to
Removal of the Catheter develop. Minor complications (3% to 5% complication rate)
include pain, infection of the skin insertion site, transient bac-
Early removal of the drainage catheter is one of the more com- teremia, and malfunction of the catheter secondary to kink-
mon causes of postprocedural morbidity and mortality. There- ing, dislodgement, or clogging with debris, such as blood clots.
fore, it is essential for the interventional radiologist to be famil- Pain can be minimized by judicious use of analgesics. Daily
iar with guidelines for catheter removal. The most important catheter evaluation by the interventional staff can serve to re-
factor to consider prior to drain removal is the clinical status duce catheter malfunction. Mortality from the procedure, usu-
of the patient. The patients condition should improve signif- ally related to sepsis or organ failure, compares favorably with
icantly within 24 to 48 hours after catheter removal [3,6,10]. the surgical literature rates of 10% to 20% [31]. The recur-
The percutaneous drainage catheter should remain in place un- rence rate following abscess drainage has been estimated to be
til the cavity is undetectable on imaging and the volume of between 5% and 10%. Recurrence may be due to early catheter
drainage is less than 10 cc on two consecutive days. Daily removal, failure to completely drain a loculated collection or
rounds by the interventional staff should carefully assess the fistulous communication with the bowel, pancreatic duct, or
patient for resolution of fever, absence of elevated white blood biliary system. Fistulas should be suspected if there is high out-
cell count, or other signs of clinical improvement. If the pa- put from the catheter (>50 mL per day) or the drainage fluid
tient fails to respond to treatment, the catheter should be ex- contains feculent material. When the patient fails to respond
amined to rule out displacement or kinking. Continuous high to treatment or sepsis is not resolving, repeat imaging with CT
drainage (>50 mL per day) should alert the radiologist for or ultrasound should be performed to determine the cause. Re-
a possible fistulous tract to bowel, pancreas, or biliary tree, peat drainage of these cavities has been shown to be successful
and the appropriate imaging modality should be used for fur- in 50% of patients with the need for surgical drainage reduced
ther evaluation [8,30]. Catheter removal is achieved by cut- by half [3,32].
ting or untying the string that fixates the locking device in In conclusion, image-guided percutaneous drainage has
place. been established as the first-line treatment for sterile or infected
Follow-up imaging on simple collections is typically not fluid collections in the abdomen and pelvis. Awareness of the
required; however, enteric or complex collections should be advantages and limitations of the procedure together with an
evaluated with CT or an abscessogram (Fig. 22.2) prior to dis- integrated management approach between interventional and
charge to document resolution or decreased size of the abscess critical care staff will serve to benefit the patient and improve
cavity. clinical outcomes.

References
1. Bufalari A, Giustozzi G, Moggi L: Postoperative intraabdominal abscesses: 12. vanSonnenberg E, Gerhard R, Wittich MD, et al: Percutaneous abscess
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2. vanSonnenberg E, Ferrucci JT, Mueller PR, et al: Percutaneous drainage of 13. Walser E, Raza S, Hernandez A, et al: Sonographically guided transgluteal
abscesses and fluid collections: technique, results and applications. Radiol- drainage of pelvic abscesses. Am J Roentgenol 181:498, 2003.
ogy 142:1, 1982. 14. Kuligowska E, Keller E, Ferrucci JT: Treatment of pelvic abscesses: value
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Interventional Radiology. Philadelphia, PA, Current Medicine, 1995. 15. Sudakoff GS, Lundeen SJ, Otterson MF: Transrectal and transvaginal sono-
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that are difficult to drain: a new approach. Radiology 147:57, 1983. Ultrasound Q 21:175, 2005.
5. Krebs TL, Daly B, Wong JJ, et al: Abdominal and pelvis therapeutic proce- 16. vanSonnenberg E, Mueller PR, Ferrucci JT Jr: Percutaneous drainage of 250
dures using CT-fluoroscopic guidance. Semin Intervent Radiol 16:191, 1999. abdominal abscesses and fluid collections. Part I. Results, failures, and com-
6. Harisinghani MG, Gervais DA, Hahn PF, et al: CT-guided transgluteal plications. Radiology 151:337, 1984.
drainage of deep pelvic abscesses: indications, technique, procedure-related 17. Lambiase RE, Deyoe L, Cronan JJ, et al: Percutaneous drainage of 335 con-
complications, and clinical outcome. RadioGraphics 22:1353, 2002. secutive abscesses: results of primary drainage with 1-year follow-up. Radi-
7. Yeung E: Percutaneous abdominal biopsy, in Allison DJ, Adam A (eds): Bal- ology 184:167, 1992.
lieres Clinical Gastroenterology. London, Balliere Tindall, 1992, p 219. 18. Jacobs D: Diverticulitis. N Engl J Med 357:2057, 2007.
8. vanSonnenberg E, Wing VW, Casola G, et al: Temporizing effect of percuta- 19. Kearon C, Hirsh MD: Management of Anticoagulation before and elective
neous drainage of complicated abscesses in critically ill patients. AJR Am J surgery. N Engl J Med 336(21):1506, 1997.
Roentgenol 142:821, 1984. 20. Douketis JD, Berger PB, Dunn AS, et al: The perioperative management of
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1997. induced neuropathy. JAMA 295(23):2765, 2006.
10. Siewert B, Tye G, Kruskal J, et al: Impact of CT-guided drainage in the 22. Appelbaum PS, Grisso T: Assessing patients capacities to consent to treat-
treatment of diverticular abscesses: size matters. Am J Roentgenol 186:680, ment. N Engl J Med 319(25):1635, 1988.
2006. 23. Palmon SC, Lloyd AT, Kirsch JR: The effect of needle gauge and lidocaine
11. Walser EM, Nealon WH, Marroquin S, et al: Sterile fluid collections in pan- pH on pain during intradermal injection. Anesth Analg 86:379, 1998.
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P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 23: Cardiopulmonary Resuscitation 181

25. vanSonnenberg E, Mueller PR, Ferrucci JT, Jr: Percutaneous drainage of 250 29. Lahorra JM, Haaga JR, Stellato T, et al: Safety of intracavity urokinase with
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26. vanSonnenberg E, Mueller P, Ferrucci JT, et al. Sump pump catheter for per- and pelvic abscesses on CT is associated with drainability. Am J Roentgenol
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228:701, 2003. 32. Gervais DA, Ho CH, ONeill MJ, et al: Recurrent abdominal and pelvic ab-
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CHAPTER 23 CARDIOPULMONARY
RESUSCITATION
BRUCE GREENBERG AND JOHN A. PARASKOS

of vital signs may be reversed is often referred to as clinical


HISTORY death. If ventilation and circulation are not restored before
irreversible damage to vital structures occurs, then irreversible
Since the introduction of cardiopulmonary resuscitation death occurs. This is referred to as biologic death. In difficult
(CPR), we have been forced to rethink our definitions of life and circumstances, the best single criterion (medical and legal) for
death. Although sporadic accounts of attempted resuscitations the ultimate death of the functioning integrated human indi-
are recorded from antiquity, until recently no rational quar- vidual (i.e., the person) is brain death [9,10]. By this criterion,
rel could be found with the sixth-century BC poetic fragment we can make decisions as to the appropriateness of continuing
of Ibycus, You cannot find a medicine for life once a man life-sustaining techniques.
is dead [1]. Until 1960, successful resuscitation was largely
limited to artificial ventilation for persons who had undergone
respiratory arrest due to causes such as near-drowning, smoke
inhalation, and aspiration. Such attempts were likely to succeed EFFICACY
if performed before cardiac arrest had resulted from hypoxia
and acidosis. Emergency thoracotomy with open heart mas- The value of standardized CPR continues to undergo consider-
sage was rarely resorted to and was occasionally successful able scrutiny. Unfortunately, it appears that its efficacy is lim-
if definitive therapy was readily available [2]. Electric rever- ited (Table 23.1). CPR does not seem to go beyond short-term
sal of ventricular fibrillation (VF) by externally applied elec- sustenance of viability until definitive therapy can be adminis-
trodes was described in 1956 by Zoll et al. [3]. This ability tered. This was the stated goal of Kouwenhoven et al. [6]. The
to reverse a fatal arrhythmia without opening the chest chal- benefit of rapid initiation of CPR has been demonstrated in
lenged the medical community to develop a method of sus- numerous studies [1114]. Data from prehospital care systems
taining adequate ventilation and circulation long enough to in Seattle showed that 43% of patients found in VF were dis-
bring the electric defibrillator to the patients aid. By 1958, charged from the hospital if CPR (i.e., BLS) was applied within
adequate rescue ventilation became possible with the devel- 4 minutes and defibrillation (i.e., ACLS) within 8 minutes. If the
opment of the mouth-to-mouth technique described by Safar onset of CPR is delayed, or if the time to defibrillation is longer
et al. [4] and Elam et al. [5]. In 1960, Kouwenhoven et al. [6] than 10 minutes, the probability is greater that the patient will
described closed chest cardiac massage, thus introducing the be in asystole or in fine VF and will convert to asystole. Survival
modern era of CPR. The simplicity of this techniqueall that decreases as each minute passes without return of spontaneous
is needed are two handshas led to its widespread dissem- circulation (ROSC).
ination. The interaction of this technique of sternal compres- Even though patients experiencing cardiac arrest in the hos-
sion with mouth-to-mouth ventilation was developed as basic pital can be expected to receive CPR and definitive therapy well
CPR. The first national conference on CPR was sponsored within the 4- and 8-minute time frames, the outcomes of in-
by the National Academy of Sciences in 1966 [7]. Instruc- hospital cardiac arrests are poor (Table 23.1).
tion in CPR for both professionals and the public soon fol- Recognizing the importance of early defibrillation, it is im-
lowed through community programs in basic life support (BLS) perative that all first-response systems provide defibrillation,
and advanced cardiac life support (ACLS). Standards for both by either using emergency medical technicians capable of per-
BLS and ACLS were set in 1973 [8] and have been updated forming defibrillation or equipping and training emergency
periodically. personnel with automatic or semiautomatic defibrillators [26].
For individuals with adequately preserved cardiopulmonary The development of inexpensive, small, lightweight, easy-to-
and neurologic systems, the cessation of breathing and car- use, voice-prompted defibrillators allows early access to de-
diac contraction may be reversed if CPR and definitive care fibrillation, before the arrival of emergency medical services
are quickly available. The short period during which the loss (EMS). Where these have been made available, and where first
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182 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 2 3 . 1
EXPERIMENTAL AND ALTERNATE TECHNIQUES OF CARDIOPULMONARY RESUSCITATION (CPR)

Researcher [Reference] Technique Notes

Taylor et al. [15] Longer compression Proposed use of longer duration to 40%50% of the duration
compressionrelaxation cycle
Chandra et al. [14,16] Simultaneous chest compression High airway pressures of 60110 mm Hg are used to augment
and lung inflation carotid flow, requiring intubation and a mechanical ventilator. Its
use has not met with universal success
Harris et al. [17] Abdominal binding Abdominal binding increases intrathoracic pressure by redistributing
blood into the thorax during CPR. Studies have demonstrated
adverse effects on coronary perfusion, cerebral oxygenation, and
canine resuscitation
Redding [18]
Koehler et al. [19]
Chandra et al. [20]
Ralston et al. [21] Interposed abdominal Abdominal compression is released when the sternum is compressed.
Higher oxygen delivery and cerebral and myocardial blood flows
are reported. One study suggests an improved survival and
neurologic outcome
Barranco et al. [22] Simultaneous chest Simultaneous chest and abdominal compression provided higher
intrathoracic pressures in compression in humans
Maier et al. [23] High-impulse CPR At compression rates of 150/min (with moderate force and brief
duration), cardiac output in dogs increased as the coronary flow
remained as high as 75% of prearrest values. High impulse and
high compression rates can result in rescuer fatigue and increased
injury
Cohen et al. [24] Active compression Forceful rebound using a plunger-like device resulted in improved
hemodynamics. Clinical results are equivocal
Halperin et al. [25] Vest inflation Circumferential chest pressure with an inflatable vest showed
improved hemodynamics and survival in dogs

responders have been trained in their use, survival rates have CPR. Indeed, it is possible that several mechanisms are opera-
been dramatically improved [27]. tive, which of these is most important may vary according to a
Although the current approach is modestly successful for patients size and chest configuration.
VF, CPR techniques have most likely not yet been optimized,
and further improvement is greatly needed. Cardiac output has
been measured at no better than 25% of normal during conven-
tional CPR in humans [28]. In animal models, myocardial per- Cardiac Compression Theory
fusion and coronary flow have been measured at 1% to 5% of
In 1960, when Kouwenhoven et al. [6] reported on the ef-
normal [29]. Cerebral blood flow has been estimated to be 3%
ficacy of closed chest cardiac massage, most researchers ac-
to 15% of normal when CPR is begun immediately [30], but
cepted the theory that blood is propelled by compressing the
it decreases progressively as CPR continues [31] and intracra-
heart trapped between the sternum and the vertebral columns.
nial pressures rise. Despite these pessimistic findings, complete
According to this theory, during sternal compression, the intra-
neurologic recovery has been reported in humans even after
ventricular pressures would be expected to rise higher than the
prolonged administration of CPR [32].
pressures elsewhere in the chest. With each sternal compres-
Researchers continue to evaluate new approaches and tech-
sion, the semilunar valves would be expected to open and the
niques, and further refinements in the delivery of CPR can be
atrioventricular (AV) valves to close. With sternal release, the
expected. Although research in improved CPR techniques and
pressure in the ventricles would be expected to fall and the AV
devices should be encouraged, research in this field is difficult.
valves to open, allowing the heart to fill from the lungs and sys-
Animal models vary, and animal data may not be valid in hu-
temic veins. Indeed, a transesophageal echocardiographic study
mans. Before new CPR techniques can be adopted, they must
in humans also supports this theory [33]. If the cardiac com-
have been demonstrated, ideally in humans, to improve either
pression mechanism were operative, ventilation would best be
survival or neurologic outcome.
interposed between sternal compressions so as not to interfere
with cardiac compression. Also, the faster the sternal compres-
sion, the higher the volume of blood flow, assuming that the
MECHANISMS OF BLOOD FLOW ventricles could fill adequately. The theory of cardiac compres-
DURING RESUSCITATION sion was first brought into question in 1962, when Weale and
Rothwell-Jackson [34] demonstrated that during chest com-
Any significant improvement in CPR technique would seem to pression, there is a rise in venous pressure almost equal to that
require an understanding of the mechanism by which blood of the arterial pressure. The following year, Wilder et al. [35]
flows during CPR. However, there is no unanimity among re- showed that ventilating synchronously with chest compression
searchers in this area. It is of interest that significant advances produced higher arterial pressures than alternating ventilation
seem to have been made by research groups holding very differ- and compression. It was more than a decade, however, before
ent ideas concerning the basic mechanism of blood flow during more data confirmed these initial findings.
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Chapter 23: Cardiopulmonary Resuscitation 183

Thoracic Pump Theory EXPERIMENTAL AND


In 1976, Criley et al. [36] reported that during cardiac ar-
ALTERNATIVE
rest, repeated forceful coughing is capable of generating sys- TECHNIQUES OF CPR
tolic pressures comparable with those of normal cardiac ac-
tivity. This finding strongly suggested that high intrathoracic Several experimental and alternate techniques of CPR are pre-
pressures are capable of sustaining blood flow, independent of sented in Table 23.2 [14,1925].
sternal compression. Subsequently, Niemann et al. [37,39] pro-
posed that the propulsion of blood during sternal compression
is due to the same mechanism of increased intrathoracic pres- Interposed Abdominal Compression CPR
sure. Studies using pressure measurements [13] and angiogra-
phy [39] support this hypothesis, as do most echocardiographic Interposed abdominal compression CPR was developed by Ral-
studies [40]. According to this theory, the heart serves as a ston et al. [21] and Babbs et al. [41]. This technique includes
conduit only during CPR. Forward flow is generated by a pres- manual compression of the abdomen by an extra rescuer during
sure gradient between intrathoracic and extrathoracic vascular the relaxation phase of chest compression (Fig. 23.1). The mid-
structures. Flow to the arterial side is favored by functional ve- abdomen is compressed at a point halfway between the xiphoid
nous valves and greater compressibility of veins, compared to process and the umbilicus with a force of approximately
arteries, at their exit points from the thorax. The thoracic pump 100 mm Hg of external pressure. This pressure is estimated
theory provides the rationale for experimental attempts at aug- to be equivalent to that required to palpate the aortic pulse in
menting forward flow by increasing intrathoracic pressure. a subject with a normal pulse. Two randomized clinical trials

TA B L E 2 3 . 2
SUMMARY OF BASIC LIFE SUPPORT ABCD MANEUVERS FOR INFANTS, CHILDREN, AND ADULTS (NEWBORN
INFORMATION NOT INCLUDED)

Adult Child
Infant
Lay rescuer: 8 y Lay rescuers: 18 y
Maneuver HCP: adolescent and older HCP: 1 yadolescent Younger than 1 y of age

Airway Head tiltchin lift (HCP: suspected trauma, use jaw thrust)
Breathing: initial 2 breaths at 1 s/breath 2 effective breaths at 1 s/breath
HCP: rescue breathing 1012 breaths/min (approximate) 1220 breaths/min (approximate)
without chest
compressions
HCP: rescue breaths for 810 breaths/min (approximate)
CPR with advanced
airway
Foreign body airway Conscious: abdominal thrusts Infant conscious: back slaps
obstruction and chest thrusts
Unconscious: CPR Infant unconscious: CPR
Circulation HCP: pulse Carotid Brachial or femoral
check (10 s)
Compression landmarks Lower half of the sternum, between nipples Just below the nipple line
(lower half of the sternum)
Compression method: Heel of one hand, other hand on top Heel of one hand or as for adults Two or three fingers
Push hard and fast
Allow complete recoil HCP (two rescuers): two
thumbencircling hands
Compression depth 11/22 in Approximately one-third to one-half the depth of the chest
Compression rate Approximately 100/min
Compression-to-ventilation 30:2 (one or two rescuers) 30:2 (single rescuer)
ratio HCP: 15:2 (two rescuers)
Defibrillation: AED Use adult pads Use AED after 5 cycles of No recommendation for
Do not use child pads CPR (out of hospital) infants <1 y of age
Use pediatric system for
children 18 y if available
HCP: for sudden collapse
(out of hospital)
or in-hospital arrest use AED
as soon as available

Note: Maneuvers used by only health care providers are indicated by HCP. AED, automatic external defibrillator.
Adapted from ECC Committee, Subcommittees and Task Forces of the American Heart Association: 2005 American Heart Association Guidelines for
Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 112[24, Suppl]:IV1203, 2005.
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184 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

to artificial circulation. It is an indispensable adjunct to car-


diac surgery and is being used more frequently for invasive
procedures as a standby in case of sudden cardiac collapse.
In dog models, bypass has been shown capable of providing
near-normal end-organ blood flow with improved ability to
resuscitate and neurologic status [47]. Emergency bypass can
be instituted with femoral artery and vein access, without tho-
racotomy [48]. Lack of study in humans, timely access, and
cost are issues to consider before bypass can be recommended
for wider use in cardiac arrest.

INFECTIOUS DISEASES AND CPR


The fear provoked by the spread of human immunodeficiency
virus (HIV) may lead to excessive caution when dealing with
strangers. The effect of this fear on CPR is serious and must be
addressed at some length [49].
The publics fear can be counteracted only by continued
education and by stressing the facts. Health care workers have
FIGURE 23.1. Interposed abdominal compression cardiopulmonary
more opportunities for exposure to patients with HIV and their
resuscitation. It is more convenient when the interposed chest and ab-
dominal compressions are performed from opposite sides of the pa- concerns must be adequately addressed [50].
tient. [From Guidelines 2000 for cardiopulmonary resuscitation and Saliva has not been implicated in the transmission of HIV
emergency cardiovascular care. Circulation 102[Suppl 8]:I-1, 2000, even after bites, percutaneous inoculation, or contamination of
with permission. Copyright 2000, American Heart Association.] open wounds with saliva from HIV-infected patients [51,52].
Hepatitis Bpositive saliva has also not been demonstrated
to be infectious when applied to oral mucus membranes or
have demonstrated a statistically significant improvement in through contamination of shared musical instruments or CPR
outcome measures for in-hospital cardiac arrest [42,43], but no training manikins used by hepatitis B carriers. However, it is
improvement has been shown for out-of-hospital arrest [44]. not impossible that the mouth-to-mouth technique may result
On the basis of these findings, interposed abdominal compres- in the exchange of blood between the patient and the res-
sion CPR is recommended as an option for in-hospital cardiac cuer if there are open lesions or trauma to the buccal mucosa
arrest when sufficient personnel trained in the technique are or lips. Diseases such as tuberculosis, herpes, and respiratory
available. However, it should be emphasized that the safety and viral infections are potentially spread during mouth-to-mouth
efficacy of interposed abdominal compression CPR in patients ventilation. Infections thought to have been transmitted by
with recent abdominal surgery, pregnancy, or aortic aneurysm CPR include Helicobacter pylori, Mycobacterium tuberculo-
has not been studied. sis, meningococcus, herpes simplex, Shigella, Streptococcus,
Salmonella, and Neisseria gonorrhoeae. There have been no
cases reported of transmission of HIV, hepatitis B virus, hep-
atitis C virus, or cytomegalovirus. The impact of these facts
Open-Chest CPR is different for lay people and health care professionals, and
One of the first forms of successful CPR was open-chest different for those carrying infection and for those at risk of
CPR. It was shown to be effective when definitive care was infection [53].
rapidly available and is associated with survival rates, largely in
operating room arrests, ranging from 16% to 37% [2]. Mech-
anistically, open-chest CPR clearly involves cardiac compres- Implications for Rescuers With Known or
sion without use of a thoracic gradient. Weale and Rothwell- Potential Infection
Jackson [34] demonstrated lower venous pressures and higher
arterial pressures than with closed-chest compression. There is Potential rescuers who know or highly suspect that they are in-
considerable evidence that open-chest CPR may be more effi- fected with a serious pathogenic organism should not perform
cacious than closed-chest CPR in terms of cardiac output and mouth-to-mouth ventilation if another rescuer is available who
cerebral and myocardial preservation. One study has suggested is less likely to be infectious or if the circumstances allow for
increased ROSC with open-chest CPR [45]. Clearly, some pa- any other immediate and effective method of ventilation, such
tients with penetrating chest trauma are not likely to respond as using mechanical ventilation devices.
to chest compression and are candidates for open-chest CPR.
Several studies suggest a benefit from thoracotomy in these pa-
tients [46]. If open-chest CPR is to be used, it should be used
early in the sequence. Patients with blunt chest and abdominal
Implications for Health Care Professionals
trauma may also be candidates for open-chest CPR. Obviously, Although the probability of a rescuer becoming infected with
this technique should not be attempted unless adequate facili- HIV during CPR seems minimal, all those called on to provide
ties and trained personnel are available. CPR in the course of their employment should have ready ac-
cess to mechanical ventilation devices. Bagvalvemask devices
should be available as initial ventilation equipment, and early
Cardiopulmonary Bypass endotracheal intubation should be encouraged when possible.
for Unresponsive Arrest Masks with one-way valves and plastic mouth and nose covers
with filtered openings are available and provide some protec-
Cardiopulmonary bypass is certainly not a form of routine life tion from transfer of oral fluids and aerosols. S-shaped mouth-
support; however, it has been considered as a possible adjunct pieces, masks without one-way valves, and handkerchiefs
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Chapter 23: Cardiopulmonary Resuscitation 185

provide little, if any, barrier protection and should not be con- The skills necessary to perform adequately during a car-
sidered for routine use. With these guidelines in mind, health diac or respiratory arrest and to interface smoothly with ACLS
care professionals are reminded that they have a special moral techniques cannot be learned from reading texts and manu-
and ethical, and in some instances legal, obligation to provide als. CPR courses taught according to AHA guidelines allow
CPR, especially in the setting of their occupational duties. hands-on experience that approximates the real situation and
tests the psychomotor skills needed in an emergency. All those
who engage in patient care should be trained in BLS. Those
whose duties require a higher level of performance should be
Implications for Manikin Training in trained in ACLS as well. As these skills deteriorate with disuse,
Cardiopulmonary Resuscitation they need to be updated. It is worth noting that there is no
certification in BLS or ACLS. Issuance of a card is neither
The guidelines of the American Heart Association (AHA) spec- a license to perform these techniques nor a guarantee of skill,
ify that students or instructors should not actively participate but simply an acknowledgment that an individual attended a
in CPR training sessions with manikins if they have derma- specific course and passed the required tests. If employers or
tologic lesions on their hands or in oral or circumoral areas, government agencies require such a card of their health work-
if they are known to be infected with hepatitis or HIV, or if ers, it is by their own mandate.
they have reasons to believe that they are in the active stage The ensuing discussion of BLS and ACLS techniques follows
of any infectious process. In routine ventilation training, in- the recommendations and guidelines established by the AHA
structors should not allow participants to exchange saliva by and presented in a supplement to volume 112 of Circulation
performing mouth-to-mouth ventilation in sequence without [57].
barrier mouthpieces. Special plastic mouthpieces and special-
ized manikins protect against such interchange of mucus.

BASIC LIFE SUPPORT FOR


Training in CPR for People ADULTS WITH AN
With Chronic Infections UNOBSTRUCTED AIRWAY
If a potentially infectious person is to be trained in CPR, com- BLS is meant to support the circulation and respiration of those
monsense precautions should be taken to protect other par- who have experienced cardiac or respiratory arrest. After rec-
ticipants from any risk of infection. The chronically infected ognizing and ascertaining its need, definitive help is summoned
individual should be given a separate manikin for practice that without delay and CPR is initiated.
is adequately disinfected before anyone else uses it. The chron-
ically infected trainee should be made aware of the preceding
guidelines for potential rescuers with infections. In addition,
the potential risk of infection for the immunocompromised res- Respiratory Arrest
cuer should not be ignored.
An agency that requires successful completion of a CPR Respiratory arrest may result from airway obstruction, near-
course as a prerequisite for employment must decide whether drowning, stroke, smoke inhalation, drug overdose, electrocu-
to waive its requirement for an employee who is unable to tion, or physical trauma. In the ICU, pulmonary congestion,
complete a CPR course for whatever reason. That agency must respiratory distress syndrome, and mucus plugs are frequent
also determine whether a chronically infected person should causes of primary respiratory arrests. The heart usually con-
continue to work in a situation in which CPR administration tinues to circulate blood for several minutes, and the residual
is a duty of employment. oxygen in the lungs and blood may keep the brain viable. Early
intervention by opening the airway and providing ventilation
may prevent cardiac arrest and may be all that is required to re-
store spontaneous respiration. In the intubated patient, careful
STANDARD PROCEDURES suctioning of the airway and attention to the ventilator settings
AND TEAM EFFORT are required.

The distinctive function of the intensive care unit (ICU) is to


serve as a locus of concentrated expertise in medical and nurs-
ing care, life-sustaining technologies, and treatment of complex Cardiac Arrest
multiorgan system derangement. Historically, it was the devel-
opment of effective treatment for otherwise rapidly fatal ar- Cardiac arrest results in rapid depletion of oxygen in vital
rhythmias during acute myocardial infarction that impelled the organs. After 6 minutes, brain damage is expected to occur,
medical community to establish ICUs [54]. Rapid response by except in cases of hypothermia (e.g., near-drowning in cold
medical personnel has been facilitated by constant professional water). Therefore, early bystander CPR (within 4 minutes) and
attendance and the development of widely accepted guidelines rapid ACLS with attempted defibrillation (within 8 minutes)
for resuscitation. Each member of the professional team is are essential in improving survival and neurologic recovery
expected to respond in accordance with these guidelines. rates [58].
Avoiding the need for CPR and ACLS by early intervention The sequence of steps in CPR may be summarized as
is a goal of rapid response teams (RRT). RRT, also called med- the ABCs of CPR: airway, breathing, and circulation. This
ical evaluation teams (MET), have been consistently shown to mnemonic is useful in teaching the public, but it should be
decrease hospital code rates [55]. Some studies have found a remembered that each step is preceded by assessment of the
decrease in hospital mortality with the use of RRT, though this need for intervention: before opening the airway, the rescuer
has not been found in all studies. How RRT can best be or- determines unresponsiveness; before breathing, the rescuer de-
ganized and implemented, as well as which hospitals benefit termines breathlessness; before circulation, the rescuer deter-
most, is yet to be determined [56]. mines pulselessness (Table 23.2).
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186 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

Assessment and Determination of


Unresponsiveness and Alerting
of Emergency Medical Services
A person who has undergone cardiac arrest may be found in
an apparently unconscious state (i.e., an unwitnessed arrest) or
may be observed to suddenly lapse into apparent unconscious-
ness (i.e., a witnessed arrest). In either case, the rescuer must
react promptly to assess the persons responsiveness by attempt-
ing to wake and communicate with the person by tapping or
gently shaking and shouting. The rescuer should summon the
nearby staff for help. If no other person is immediately avail-
able, the rescuer should call the hospital emergency line for the
resuscitation team to respond (e.g., code blue).
In the ICU, nearly all arrests should be witnessed. Early
recognition of cardiac and respiratory arrests is facilitated by FIGURE 23.2. The patient must be supine on a firm, flat surface.
electronic and video monitoring. Unfortunately, it is quite pos- [From Guidelines for cardiopulmonary resuscitation and emergency
sible for a patient to become lost behind this profusion of elec- cardiac care. Emergency Cardiac Care Committee and Subcommittees,
tronic signals, the dependability of which varies widely. For American Heart Association. JAMA 268:2171, 1992, with permission.
several precious minutes, a heart with pulseless electric activ- Copyright 1992, American Medical Association.]
ity (PEA) continues to provide a comforting electronic signal,
while the brain suffers hypoxic damage. A high frequency of
false alarms due to loose electrodes or other artifacts may dan- airway and check for spontaneous breathing (see Chapter 1).
gerously raise the threshold of awareness and prolong the re- In a monitored arrest with VF or tachycardia, this step is taken
sponse time of the ICU team. The overall efficacy of the mon- after initial attempts to defibrillate. Meticulous attention to es-
itoring devices, therefore, depends highly on meticulous skin tablishing an airway and supplying adequate ventilation is es-
preparation and care of electrodes, transducers, pressure ca- sential to any further resuscitative effort. The team leader must
bles, and the like. carefully monitor the adequacy of ventilation, as well as direct
Sudden apparent loss of consciousness, occasionally with the resuscitative effort. The leadership role is best accomplished
seizures, may be the first signal of arrest and requires prompt if the leader does not directly perform procedures.
reaction. After determining unresponsiveness, the pulse is as- The head tiltchin lift maneuver (Figs. 23.3 and 23.4) is usu-
sessed. If the carotid pulse cannot be palpated in 5 to 10 sec- ally successful in opening the airway. The head is tilted back-
onds and a defibrillator is not immediately available, a pre- ward by a hand placed on the forehead. The fingers of the other
cordial thump can be considered and is performed by striking hand are positioned under the mandible and the chin is lifted
the lower third of the sternum with the fist, from a height of upward. The teeth are almost approximated, but the mouth is
approximately 8 in (or the span of the stretched fingers of one not allowed to close. Because considerable cervical hyperex-
hand). However, there is a lack of evidence supporting its use. tension occurs, this method should be avoided in patients with
The thump should not be performed by BLS providers and cervical injuries or suspected cervical injuries. The jaw-thrust
the AHA has not recommended for or against its use [57]. maneuver (Fig. 23.5) provides the safest initial approach to
If the pulse does not return and a defibrillator is not immedi- opening the airway of a patient with a cervical spine injury;
ately available, the rescuer should proceed with establishing the it usually allows excellent airway opening with a minimum of
airway (see the next section). cervical extension. The angles of the mandible are grasped us-
ing both hands and lifting upward, thus tilting the head gently
backward.
Opening the Airway and After opening the airway, the rescuer should take 3 to
Determining Breathlessness 5 seconds to determine if there is spontaneous air exchange.
This is accomplished by placing an ear over the patients mouth
After establishing unresponsiveness and positioning the indi- and nose while watching to see if the patients chest and ab-
vidual on his or her back (Fig. 23.2), the next step is to open the domen rise and fall (look, listen, and feel; see Fig. 23.4). If

FIGURE 23.3. Opening the airway.


A: Airway obstruction caused by
tongue and epiglottis. B: Opening the
airway with the head tiltchin lift
maneuver. [From BLS for Healthcare
Providers, American Heart Associa-
tion, 2006, with permission. Copy-
A B right 2006, American Heart Associa-
tion.]
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Chapter 23: Cardiopulmonary Resuscitation 187

FIGURE 23.4. Determining breathlessness.


Open the airway and look, listen, and feel.
[From BLS for Healthcare Providers, Amer-
ican Heart Association, 2006, with permis-
sion. Copyright 2006, American Heart Asso-
ciation.]

the rescuer fails to see movement, hear respiration, or feel the patients lungs to deflate between breaths. Thereafter, the rate
rush of air against the ear and cheek, rescue breathing should of 10 to 12 breaths per minute is maintained for as long as
be initiated. necessary, with tidal volumes of approximately 700 mL. De-
livering the breath during 1 second helps to prevent gastric
insufflation compared with faster delivery. Melker et al. [59]
Rescue Breathing demonstrated airway pressures well in excess of those required
to open the lower esophageal sphincter when quick breaths are
If spontaneous breathing is absent, rescue breathing with an used to ventilate patients. If the patient wears dentures, they are
airwaymaskbag unit must be initiated (see Chapter 1). If usually best left in place to assist in forming an adequate seal.
equipment is immediately available and the rescuer is trained, If air cannot be passed into the patients lungs, another at-
intubation and ventilatory adjuncts should be used initially. tempt at opening the airway should be made. The jaw-thrust
Each breath should be delivered during 1 second, allowing the maneuver may be necessary. If subsequent attempts at venti-
lation are still unsuccessful, the patient should be considered
to have an obstructed airway and attempts should be made to
dislodge a potential foreign body obstruction.

Determining Pulselessness
In the adult, the absence of a central pulse is best determined
by palpating the carotid artery (Fig. 23.6), although rarely the
carotid pulse may be absent because of localized obstruction.
If a pulse is not felt after 10 seconds of careful searching, chest
compression is initiated, unless electric countershock for ven-
tricular arrhythmia or artificial pacing for asystole is immedi-
ately available. Although lay rescuers are no longer expected to
perform a pulse check because it has been shown that checking
the carotid pulse by a lay person is an inaccurate method of
confirming the presence or absence of circulation, it is the po-
sition of the AHA that health care providers should continue
to be taught and to perform a pulse check. Therefore, rescuers
should start CPR if the victim is unconscious (unresponsive),
not moving and not breathing [60].

FIGURE 23.5. Jaw-thrust maneuver: opening the airway with min- Chest Compression
imal extension of the neck. [From BLS for Healthcare Providers,
American Heart Association, 2006, with permission. Copyright 2006, Artificial circulation depends on adequate chest compression
American Heart Association.] through sternal depression. Recent recommendations of CPR
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188 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

A B

FIGURE 23.6. Determining pulselessness. A: Feeling the laryngeal cartilage. B: Fingers slide into groove
between trachea and sternocleidomastoid muscle, searching for carotid pulse. [From BLS for Health-
care Providers, American Heart Association, 2006, with permission. Copyright 2006, American Heart
Association.]

are push hard at a rate of 100 compressions per minute, allow


full chest recoil, and minimize interruptions in chest compres-
sions [60]. The safest manner of depressing the sternum is
with the heel of the rescuers hand at the nipple line, with the
fingers kept off the rib cage (Fig. 23.7). It is usually most ef-
fective to cover the heel of one hand with the heel of the other,
the heels being parallel to the long axis of the sternum. If the
rescuers hands are placed either too high or too low on the
sternum, or if the fingers are allowed to lie flat against the rib
cage, broken ribs and organ laceration can result. Although it
is important to allow the chest to recoil to its normal position
after each compression, it is not advisable to lift the hands from
the chest or change their position.
The rescuers elbows should be kept locked and the arms
straight, with the shoulders directly over the patients sternum
(Fig. 23.7). This position allows the rescuers upper body to
provide a perpendicularly directed force for sternal depression.
The sternum is depressed 1.5 to 2.0 in (4 to 5 cm) at a rate of ap-
proximately 100 compressions per minute. In large patients, a
slightly greater depth of sternal compression may be needed to
generate a palpable carotid or femoral pulse. At the end of each
compression, pressure is released and the sternum is allowed to
return to its normal position. Equal time should be allotted to
compression and relaxation with smooth movements, avoiding
jerking or bouncing the sternum. Manual and automatic chest
compressors are available for fatigue-free sternal compression
and are used by some EMS crews and emergency room and
ICU personnel. Whether using hinged manually operated de-
vices or compressed air-powered plungers, the rescuer must be
constantly vigilant about proper placement and adequacy of
sternal compression. An experimental device using a plunger-
like suction device may improve flow by facilitating sternal
rebound and thoracic vascular filling; this has been referred to
as active compressiondecompression CPR.
Ventilation and sternal compression should not be inter-
rupted except under special circumstances. Warranted inter-
ruptions include execution of ACLS procedures (e.g., endo-
tracheal intubation and placement of central venous lines) or
an absolute need to move the patient. Even in these limited
circumstances, interruption of CPR should be minimized. In a
retrospective analysis of the VF waveform, interruption of CPR
was associated with a decreased probability of conversion of
VF to another rhythm [61].
New data suggest that chest compression-only CPR is as ef-
fective as standard CPR (chest compression plus rescue breath- FIGURE 23.7. External chest compression. Proper position of the res-
ing) for out-of-hospital arrest [62,63]. Subgroup analysis in cuer: place heel of the hand on the breast bone at the nipple line with
one study suggested a trend for increased survival to hospital shoulders directly over the patients sternum and elbows locked. [From
discharge for chest compression-only CPR if the cause of the BLS for Healthcare Providers, American Heart Association, 2006, with
arrest was cardiac in origin or the rhythm was shockable [62]. permission. Copyright 2006, American Heart Association.]
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Chapter 23: Cardiopulmonary Resuscitation 189

Whether chest compression-only therapy supplants standard during CPR, with studies in clinical situations showing that pa-
therapy will require further research. tients are commonly ventilated at a rate of 18 to 30, far faster
than recommended. The adequacy of circulation is assessed by
noting an adequate carotid pulse with sternal compressions.
Two-Rescuer CPR Animal and clinical studies suggest that the best guides to
the efficacy of ongoing CPR efforts are aortic diastolic pres-
The combination of artificial ventilation and circulation can be sure and myocardial perfusion pressure (aortic diastolic mi-
delivered more efficiently and with less fatigue by two rescuers. nus right atrial diastolic) [6668]. In instrumented patients for
One rescuer, positioned at the patients side, performs sternal whom systemic arterial pressure (with or without central ve-
compressions, while the other, positioned at the patients head, nous pressure) is available, attempts should be made to opti-
maintains an open airway and performs ventilation. This tech- mize myocardial perfusion pressure during CPR.
nique should be mastered by all health care workers called on to Pupillary response, if present, is a good indicator of cere-
perform CPR. Lay people have not been routinely taught this bral circulation. However, fixed and dilated pupils should not
method in the interest of improving retention of basic skills. be accepted as evidence of irreversible or biologic death. Ocular
The compression rate for two-rescuer CPR, as for one-rescuer diseases, such as cataracts, and a variety of drugs (e.g., atropine
CPR, is approximately 100 compressions per minute. The new and ganglion-blocking agents) interfere with the pupillary light
recommendation of the compression-to-ventilation ratio is 30 reflex. The decision to cease BLS should be made only by the
to 2. In an animal model of cardiac arrest, a compression-to- physician in charge of the resuscitation effort; this decision
ventilation ratio of 30 to 2 was associated with significantly should not be made until it is obvious that the patients car-
shorter time to ROSC [64]. The only exception to this recom- diovascular system will not respond with ROSC to adequate
mendation is when two health care workers are providing CPR administration of ACLS, including electric and pharmacologic
to a child or infant (except newborns); in this instance, a 15 to interventions. Remediable problems such as airway obstruc-
2 compression-to-ventilation ratio should be used [60]. When tion, severe hypovolemia, and pericardial tamponade should
the rescuer performing compressions is tired, the two rescuers also have been reasonably excluded by careful attention to
should switch responsibilities with the minimum possible delay. ACLS protocols. Published guidelines in the literature suggest
that BLS can be stopped if all of the following are present: the
event was not witnessed by EMS personnel, no AED has been
used, and there is no ROSC in the prehospital setting [57].
Complications of BLS Procedures
Proper application of CPR should minimize serious compli-
cations, but serious risks are inherent in BLS procedures and PEDIATRIC RESUSCITATION
should be accepted in the context of cardiac arrest. Awareness
Most infants and children who require resuscitation have had
of these potential complications is important to the postresus-
a primary respiratory arrest. Cardiac arrest results from the
citative care of the arrest patient.
ensuing hypoxia and acidosis; therefore, the focus of pediatric
Gastric distention and regurgitation are common complica-
resuscitation is airway maintenance and ventilation. The out-
tions of artificial ventilation without endotracheal intubation.
comes for CPR in children with cardiac arrest are poor because
These complications are more likely to occur when ventilation
the cessation of cardiac activity is usually the manifestation of
pressures exceed the opening pressure of the lower esophageal
prolonged hypoxia. Brain damage is, therefore, all too com-
sphincter. In mask ventilation, 1 second should be allowed for
mon. Respiratory arrest, if treated before cessation of cardiac
air delivery. Although an esophageal obturator airway may
activity has supervened, carries a much better prognosis [69].
decrease the threat of distention and regurgitation during its
It is for this reason that it is recommended to provide the initial
use, the risk is increased at the time of its removal. To obviate
steps of CPR for infants and children before taking the time to
this risk, the trachea should be intubated and protected with
telephone for emergency assistance. The first minute of CPR
an inflated cuff before the esophageal cuff is deflated and the
will allow opening of the airway and the beginning of artificial
esophageal obturator removed.
ventilation. If an obstructed airway is found, attempts at dis-
Complications of sternal compression and manual thrusts
lodging a foreign body should not be delayed. In children with
include rib and sternal fractures, costochondral separation, flail
a history of cardiac disease or arrhythmias, or in previously
chest, pneumothorax, hemothorax, hemopericardium, subcu-
healthy children who are witnessed to have a sudden collapse,
taneous emphysema, mediastinal emphysema, pulmonary con-
a primary arrhythmic event is more likely and immediate acti-
tusions, bone marrow and fat embolism, and lacerations of the
vation of the EMS system may be beneficial.
esophagus, stomach, inferior vena cava, liver, or spleen [65].
Effective techniques for ventilation and chest compression
Although rib fractures are common during CPR, especially in
vary with the childs size. Infant procedures are applicable to
the elderly, no serious sequelae are likely unless tension pneu-
patients who are smaller than an average child of 1 year. Child
mothorax occurs and is not recognized. The more serious com-
techniques are applicable to patients who are of a size similar
plications are unlikely to occur in CPR if proper hand position
to the average child of 1 to 8 years. Adult techniques are ap-
is maintained and exaggerated depth of sternal compression is
propriate for patients who appear larger than the typical child
avoided. Overzealous or repeated abdominal or chest thrusts
of 8 years of age.
for relief of airway obstruction are more likely to cause frac-
If the child is found to be apneic, he or she is placed in the
tures or lacerations. For this reason, abdominal thrust is not
supine position and the head tiltchin lift maneuver is used to
recommended for the infant younger than 1 year.
open the airway (Fig. 23.8). Overextension of the neck is un-
necessary and is best avoided. Some believe that overextension
of the childs flexible neck may obstruct the trachea; however,
Monitoring the Effectiveness of there are no data to support this. The jaw-thrust maneuver
Basic Life Support should be used if an adequate airway is not obtained with the
head tiltchin lift maneuver or if neck injury is suspected.
The effectiveness of rescue effort is assessed regularly by the Artificial ventilation of the infant requires the rescuers
ventilating rescuer, who notes the chest motion and the es- mouth to cover both the mouth and the nose to make an effec-
cape of expired air. Unintentional hyperventilation is frequent tive seal. If the childs face is too large to allow a tight seal to
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190 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

FIGURE 23.8. Head tiltchin lift in the infant: opening the airway.
[From BLS for Healthcare Providers, American Heart Association, FIGURE 23.9. Locating finger position for sternal compression in the
2006, with permission. Copyright 2006, American Heart Association.] infant, using an imaginary line between the nipples. [From Standards
and guidelines for cardiopulmonary resuscitation (CPR) and emer-
gency cardiac care (ECC). JAMA 255:2843, 1986, with permission.
Copyright 1986, American Medical Association.]
be made over both the mouth and the nose, the mouth alone is
covered, as for the adult.
The lung volume of the pediatric patient is small enough hands technique may be used when two rescuers are available
that a puff of air from the airwaymaskbag unit apparatus (Fig. 23.10). The frequency of sternal compressions for infants
might be adequate to inflate the lungs. However, the smaller di- and children is 100 per minute. During one-rescuer support,
ameter of the tracheobronchial tree and any pulmonary disease the ratio of compression to ventilation is 30 to 2 for infants
that may be contributing to the arrest usually provide consid- and children [60].
erable resistance to airflow. Therefore, a surprising amount of
inspiratory pressure may be needed to move adequate air into
the lungs. This is especially true for the child who may have
edematous respiratory passages. Accordingly, adequacy of ven- OBSTRUCTED AIRWAY
tilation must be monitored by observing the rising and falling
An unconscious patient can experience airway obstruction
of the chest and feeling and listening for the exhaled air from
when the tongue falls backward into the pharynx. Alterna-
the childs mouth and nose. Excessive ventilatory volumes may
tively, the epiglottis may block the airway when the pharyn-
exceed esophageal opening pressure and cause gastric disten-
geal muscles are lax. In the sedated or ill patient, regurgitation
tion.
of stomach contents into the pharynx is a frequent cause of
Gastric decompression is dangerous and should be avoided
respiratory arrest. Blood clots from head and facial injuries
until the patient has been intubated and the cuff inflated to
are another source of pharyngeal and upper airway obstruc-
protect the respiratory tract from aspiration. If the gastric dis-
tion. Even otherwise healthy people may have foreign body
tention is so severe that ventilation is greatly compromised, the
obstruction from poorly chewed food, large wads of gum, and
childs body should be turned to one side before pressure on
so forth. The combination of attempting to swallow inade-
the abdomen is applied. It is preferable to use a gastric tube
quately chewed food, drinking alcohol, and laughing is partic-
with suction whenever possible.
ularly conducive to pharyngeal obstruction. Childrens smaller
The ventilation rate for infants is approximately 20 breaths
airways are likely to obstruct with small nuts or candies.
per minute (one every 3 seconds), whereas the rate for children
can be 12 to 20 breaths per minute (one every 3 to 5 seconds).
Adolescents are ventilated at the adult rate of 10 to 12 breaths
per minute (one every 5 seconds). If artificial circulation is not
necessary, more rapid ventilatory rates are acceptable.
Artificial circulation is instituted in the absence of a palpable
pulse. The pulse of the larger child can easily be detected at the
carotid artery, as in the adult. The neck of the infant, however,
is too short and fat for reliable palpation of the carotid artery.
Palpation of the precordium is also unreliable; some infants
have no precordial impulse in spite of adequate cardiac output.
It is recommended, therefore, that the presence of an infants
pulse be determined by palpating the brachial artery between
the elbow and the shoulder.
To apply chest compression in an infant, the rescuers index
finger is placed on the sternum, just below the intermammary
line. The proper area for compression is one fingerbreadth be-
low the intermammary line on the lower sternum, at the loca- FIGURE 23.10. Chest compression in the infant using the two thumb
tion of the middle and ring fingers (Fig. 23.9). Using two or encircling hands technique. (Two rescuers are required.) [From Guide-
three fingers, the sternum is compressed approximately one- lines 2000 for cardiopulmonary resuscitation and emergency cardio-
third to one-half the depth of the thorax. Alternatively, for vascular care. Circulation 102[Suppl 8]:I-1, 2000, with permission.
chest compressions in the infant, the two thumbencircling Copyright 2000, American Heart Association.]
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Chapter 23: Cardiopulmonary Resuscitation 191

Children are also prone to airway obstruction by placing toys beside or astride the persons thighs and places the heel of one
or objects such as marbles or beads in their mouths. hand against the persons abdomen, slightly above the navel
Patients who experience partial obstruction with reasonable and well below the xiphoid process. The other hand is placed
gas exchange should be encouraged to continue breathing ef- directly on top of the first and pressed inward and upward
forts with attempts at coughing. A patient whose obstruction with a quick forceful thrust. If the patient is unresponsive, CPR
is so severe that air exchange is obviously markedly impaired should be initiated.
(cyanosis with lapsing consciousness) should be treated as If attempted rescue breathing in an arrested patient fails to
having complete obstruction. move air into the lungs, an obstructed airway must be presumed
Patients who experience complete obstruction may still be to be present. It may simply be due to the tongue or epiglottis,
conscious. They are unable to cough or vocalize. A subdi- rather than a foreign body. If the airway remains closed after
aphragmatic abdominal thrust may force air from the lungs repositioning the head, other maneuvers to open the airway, in-
in sufficient quantity to expel a foreign body from the airway cluding the jaw-thrust and tongue-jaw lift, must be used. Chest
[70]. thrusts may be substituted for abdominal thrusts in patients in
If the person is still standing, the rescuer stands behind the advanced stages of pregnancy, in patients with severe ascites, or
person and wraps his or her arms around the persons waist. in the markedly obese. The fist is placed in midsternum for the
The fist of one hand is placed with the thumb side against the erect and conscious patient. For the supine patient, the hand is
persons abdomen in the midline, slightly above the umbilicus positioned on the lower sternum, as for external cardiac com-
and well below the xiphoid process (Fig. 23.11). The fist is pression. Each thrust is delivered slowly and distinctly.
grasped with the other hand and quickly thrust inward and If attempts at dislodging a foreign body or relieving airway
upward. It may be necessary to repeat the thrust six to ten obstruction fail, special advanced procedures are necessary to
times to clear the airway. Each thrust should be a separate and provide oxygenation until direct visualization, intubation, or
distinct movement. tracheostomy is accomplished.
If the patient is responsive and lying down, he or she should
be positioned face up in the supine position. The rescuer kneels

ADVANCED CARDIAC LIFE


SUPPORT IN ADULTS
The use of adjunctive equipment, more specialized techniques,
and pharmacologic and electric therapy in the treatment of a
person who has experienced cardiac or respiratory arrest is
generally referred to as ACLS. These techniques and their in-
terface with BLS and the EMS are considered in the AHAs
ACLS teaching program. An improvement in survival after
in-hospital cardiac arrest has been demonstrated after med-
ical house officers were trained in ACLS [71]. An in-depth
discussion is available in the ACLS text published by the
AHA.
The focus of the following sections is on the techniques
and medications used in the initial resuscitative efforts. The
demarcation from therapies more commonly reserved for the
ICU is often indistinct; indeed, it is expected to vary with
the experience of the prehospital team and the degree of physi-
cian supervision. In general, most ACLS measures should be
applied by trained personnel operating within an EMS system
in the community, in transport, or in the hospital setting.

Airway and Ventilatory Support


Oxygenation and optimal ventilation are prerequisites for suc-
cessful resuscitation (see Chapter 1). Supplemental oxygen
should be administered as soon as it becomes available, begin-
ning with 100%. In the postresuscitation period, the amount of
administered oxygen may be decreased as guided by the arterial
blood partial pressure of oxygen.
Emergency ventilation commonly begins with the combined
use of a mask and oral airway. Mouth-to-mask ventilation is
very effective as long as an adequate seal is maintained between
the mask and the face. Most masks are best fitted by flaring the
top and molding it over the bridge of the nose. The inflated rim
is then carefully molded to the cheeks as the mask is allowed to
recoil. Relatively firm pressure is required to maintain the seal.
FIGURE 23.11. Abdominal thrust with conscious patient standing:
Masks with one-way valves also provide a measure of isolation
rescuer standing behind individual with foreign body airway obstruc- from the patients saliva and breath aerosol. Bagvalvemask
tion. [From BLS for Healthcare Providers, American Heart Associa- ventilation requires strong hands and a self-inflating bag. The
tion, 2006, with permission. Copyright 2006, American Heart Associ- bag should be connected to a gas reservoir and to oxygen so
ation.] that 100% oxygen delivery can be approximated. It cannot
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192 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

be overemphasized that the success of this method depends be present. This alarm warns the rescuer that the patient re-
on airway patency and an adequate seal between the mask quires higher inspiratory pressures and may not be adequately
and the face. Equally important is adequate compression of ventilated. Barotrauma is likely to occur in infants and chil-
the bag to deliver the required tidal volume. It is advisable dren. Children often have high airway resistances and are diffi-
that everyone who uses this technique practice on a recording cult to ventilate with these resuscitators. These devices should
ventilating manikin to assess the adequacy of the method in his be avoided in general and should not be used with infants or
or her hands. Many people will discover that their hands are children.
not large enough or strong enough to deliver 700 mL air. Some Endotracheal intubation is required if the patient cannot
may have to squeeze the bag between their elbow and chest wall be rapidly resuscitated or when adequate spontaneous venti-
to supply adequate ventilation. If two people are available to lation does not resume quickly. Experienced personnel should
ventilate, one should secure the mask while the other uses both attempt intubation. Resuscitative efforts should not be inter-
hands to attend to the bag. rupted for more than 30 seconds with each attempt. Cricoid
The mask design should include the following features: pressure should be applied, when possible, by a second person
The use of transparent material, which allows the rescuer
during endotracheal intubation to protect against regurgita-
tion of gastric contents. The prominence inferior to that of the
to assess lip color and to observe vomitus, mucus, or other
thyroid cartilage is the cricoid cartilage. Downward pressure
obstructing material in the patients airway.

should be applied with the thumb and index finger (Fig. 23.12)
A cushioned rim around the masks perimeter to conform to
until the cuff of the endotracheal tube is inflated.
the patients face and to facilitate a tight seal.

Once the patient is intubated and the trachea is protected
A standard 15- to 22-mm connector, which allows the use
from regurgitation, faster inspiratory flow rates are possible.
of additional airway equipment.

However, hyperventilation should be avoided. Checking arte-
A comfortable fit to the rescuers hand.

rial blood gases will assist in the determination of an adequate
An oxygen insufflation inlet, which allows oxygen supple-
minute ventilation. Increasing the respiratory rate may be detri-
mentation during mouth-to-mask ventilation.

mental [72].
A one-way valve, which allows some protection during
The laryngeal mask airway (LMA) has been effective for
mouth-to-mask ventilation.

maintaining airway patency during anesthesia since 1988 and
Availability in appropriate sizes and shapes, for various-
has been accepted as one of the adjuncts for airway control
sized faces. Most adults will be accommodated by a standard
and ventilation during CPR. The LMA provides a more sta-
medium-sized (no. 4) oval-shaped mask.
ble and consistent means of ventilation than bagmask ven-
Ventilating bags must be designed to include the following tilation [73]. The current research concludes that regurgita-
features: tion is less common with LMA than with the bag-mask, and
A self-refilling bag, which allows operation independent of
although it cannot provide complete protection from aspira-
tion, it is less frequent when used as the first-line airway device
a fresh gas source.
A fresh gas inlet, which allows ambient air or supplemental
[73,74]. Multiple studies have documented the advantages of
LMA for its relative ease with insertion and ease of use by
oxygen to flow into the reservoir bag through a valve inlet.
A nipple for oxygen connection, located near the gas inlet
a variety of personnel: nurses, medical students, respiratory
therapists, and EMS, many with little prior experience using
valve.
An oxygen reservoir bag.
the device. Studies have shown that inexperienced personnel
Availability in pediatric and adult sizes.
achieved an 80% to 94% success rate on first placement at-
A nonrebreathing valve directing flow to the patient during
tempts and achieved 98% and 94% on subsequent attempts
of adult and pediatric cases, respectively. The LMA provides
inhalation and to the atmosphere during exhalation. The
adequate and effective ventilation when measured against en-
valve casing should be transparent to allow visual inspec-
dotracheal intubation [75]. Additionally, less equipment and
tion of its function. A pop-off feature is often present to
training are needed to insert the device successfully. It may also
prevent high airway pressures; however, such valves should
have advantages over the endotracheal tube when patient air-
have provision to override the pop-off feature because higher
way access is obstructed, when the patient has an unstable neck
airway pressures are sometimes required to ventilate lungs
with unusually high resistances, especially in children.
Reservoir tubing that can be attached to the fresh gas inlet
valve, which allows an accumulation of oxygen to refill the
reservoir bag during the refill cycle. Such a reservoir allows
delivered oxygen to approach 100%; without it, the self-
refilling bag can deliver only 40% to 50% oxygen.
Oxygen-powered resuscitators allow the pressure of com-
pressed oxygen tanks at 50 psi to drive lung inflation. They are
usually triggered by a manual control button, and the oxygen
can be delivered through a mask or tube for ease of ventila-
tion. These devices deliver oxygen at a flow rate of 100 L per
minute and allow airway pressures of 60 cm H2 O. However,
when used with masks and unprotected airways (not separated
from the esophagus by an inflated cuff), these devices are likely
to cause gastric distention and poor ventilation. They are not
as reliable as mouth-to-mask or valvebagmask ventilation.
When used in adults, they should be recalibrated to deliver
flows of no more than 40 L per minute to avoid opening the
lower esophageal sphincter. A relief valve that opens at ap- FIGURE 23.12. Cricoid pressure: application of downward pressure
proximately 60 cm H2 O and vents any excess volume into over the cricoid with neck extended. [From Sellick BA: Cricoid pres-
the atmosphere should be present. In addition, an alarm that sure to control regurgitation of stomach contents during induction of
sounds whenever the relief valve pressure is exceeded should anaesthesia. Lancet 2:404, 1961, with permission.]
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Chapter 23: Cardiopulmonary Resuscitation 193

vice facilitates CPR during transport. An acceptable electrocar-


diogram (ECG) can often be recorded with the compressor in
operation, and defibrillation can be delivered during the down-
stroke of chest compression, without delays in CPR.
ECG monitoring is necessary during resuscitation to guide
appropriate electric and pharmacologic therapy. Until ECG
monitoring allows diagnosis of the rhythm, the patient should
be assumed to be in VF (see the section Ventricular Fibrillation
Thyroid cartilage Thyroid gland
and Pulseless Ventricular Tachycardia).
Most defibrillators currently marketed have built-in moni-
Cricothyroid toring circuitry in the paddles or pads (quick look). On applica-
Cricoid cartilage
Membrane tion of the defibrillator paddles, the patients ECG is displayed
on the monitor screen. This facilitates appropriate initial ther-
apy. For continuous monitoring beyond the first few minutes,
a standard ECG monitoring unit should be used.
ECG monitoring must never be relied on without frequent
FIGURE 23.13. Landmarks for locating the cricothyroid membrane reference to the patients pulse and clinical condition. What
for use of transtracheal catheter ventilation or cricothyrotomy. [From appears on the monitor screen to be VF or asystole must not
Textbook of Advanced Cardiac Life Support. Chicago, American Heart be treated as such unless the patient is found to be without a
Association, 1987, with permission. Copyright American Heart Asso- pulse. An apparently satisfactory rhythm on the monitor must
ciation.] be accompanied by an adequate pulse and blood pressure.

injury, or when suitable positioning of the patient for endotra- Defibrillation


cheal intubation is unattainable. LMA insertion has been suc-
cessful when attempts at endotracheal intubation by experts Electric defibrillation is the definitive treatment for most car-
were unsuccessful [75]. Endotracheal tubes can be fiberopti- diac arrests. It should be delivered as early as possible and
cally inserted through an established LMA. repeated frequently until VF or pulseless VT has been termi-
Relative contraindications for LMA use include the patient nated.
with an increased risk of aspiration pneumonitis. Examples of Electric defibrillation involves passing an electric current
such situations include morbid obesity, pregnancy, recent food through the heart and causing synchronous depolarization of
ingestion, gastrointestinal obstruction, and hiatal hernia. De- the myofibrils. As the myofibrils repolarize, the opportunity
spite these considerations, oxygenation and ventilation during arises for the emergence of organized pacemaker activity.
cardiac arrest receive top priority and the LMA should be used Proper use of the defibrillator requires special attention to
if it is the fastest and efficient means of providing airway pa- the following:
tency.
If attempts at relieving an obstructed airway have failed, 1. Selection of proper energy levels (see the section Clinical
several advanced techniques may be used to secure the airway Settings). This lessens myocardial damage and arrhyth-
until intubation or tracheostomy is successfully performed. In mias occasioned by unnecessarily high energies. For bipha-
transtracheal catheter ventilation, a catheter is inserted over a sic defibrillators, the energy should be 120 to 200 J. For the
needle through the cricothyroid membrane (Fig. 23.13). The monophasic defibrillators, the energy should be 360 J [57].
needle is removed and intermittent jet ventilation initiated (see 2. Proper asynchronous mode. The proper mode must be se-
Chapter 1). In cricothyrotomy, an opening is made in the lected if the rhythm is VF. The synchronizing switch must
cricothyroid membrane with a knife (see Chapter 12). Tra- be deactivated or the defibrillator will dutifully await the R
cheostomy, if still necessary, is best performed in the operating wave that will never come. For rapid pulseless VT (approxi-
room by a skilled surgeon after the airway has already been mately 150 to 200 beats per minute), it is best not to attempt
secured by one of the aforementioned techniques. synchronization with the R wave because this increases the
likelihood of delivering the shock on the T wave. If the coun-
tershock should fall on the T wave and induce VF, another
Circulatory Support unsynchronized countershock must be delivered promptly
after confirming pulselessness.
Chest compression should not be unduly interrupted while ad- 3. Proper position of the paddles or pads. This allows the ma-
junctive procedures are instituted. The rescuer coordinating the jor energy of the electric arc to traverse the myocardium.
resuscitation effort must ensure that adequate pulses are gen- The anterolateral position requires that one paddle or pad
erated by the compressor. The carotid or femoral pulse should be placed to the right of the upper sternum, just below the
be evaluated every few minutes. clavicle. The other paddle or pad is positioned to the left
Mechanical chest compressors seem useful in the hands of of the nipple in the left midaxillary line. In the anteroposte-
experienced resuscitators. It is important that such devices be rior position, one paddle or pad is positioned under the left
correctly calibrated to provide a stroke of 1.5 to 2.0 in. The po- scapula with the patient lying on it. The anterior paddle or
sition of the press on the sternum must be checked frequently pad is positioned just to the left of the lower sternal border.
to ensure adequate compression with a minimum of damage. 4. Adequate contact between paddles or pads and skin. This
The press may be a manually operated hinged device or may should be ensured, using just enough electrode paste to cover
be powered by compressed gas (usually 100% oxygen). The the paddle face without spilling over the surrounding skin.
plunger is mounted on a backboard and is associated with a The rescuer should hold the paddles with firm pressure (ap-
timepressure-cycled ventilator. This device is programmed to proximately 25 lb). The pressure should be delivered using
deliver CPR using a compression duration that is 50% of the the forearms; leaning into the paddles should be avoided for
cycle length. Such units allow the patient to be harnessed to fear that the rescuer may slip. If defibrillator electrode pad-
the backboard, fixing the location of the plunger. When used dles are used, the skin must be carefully prepared according
properly, with careful monitoring of patient position, this de- to the manufacturers directions.
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194 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

5. No contact with anyone other than the patient. The rescuer In infants and children as well as adults, the intraosseous
must be sturdily balanced on both feet and not standing on a (IO) route is easy to achieve and very effective for venous access.
wet floor. CPR must be discontinued with no one remaining Special kits to achieve IO access in the adult are now available.
in contact with the patient. It is the responsibility of the per- Drugs such as epinephrine, atropine, and lidocaine can be
son defibrillating to check the patients surroundings, ensure administered via the endotracheal tube if there is delay in
the safety of all participants, loudly announce the intention achieving venous access. However, this route requires a higher
to countershock, and depress both buttons. The use of an dose to achieve an equivalent blood level [38], and a sustained
automatic or semiautomatic defibrillator does not decrease duration of action (a depot effect) can be expected if there is
the operators need for diligence. a return in spontaneous circulation [38]. It is suggested that 2.0
6. If no skeletal muscle twitch or spasm has occurred, the to 2.5 times the IV dose be administered when using the endo-
equipment, contacts, and synchronizer switch used for elec- tracheal route. Delivery of the drug to the circulation is facili-
tive cardioversions should be rechecked. tated by diluting the drug in 10 mL of normal saline or distilled
water and delivering it through a catheter positioned beyond
Electric energy delivered in a biphasic waveform is clearly the tip of the endotracheal tube. Stop chest compressions, spray
superior to monophasic waveforms for implantable defibrilla- the solution quickly down the endotracheal tube, and give sev-
tors (see Chapter 6), but there is a paucity of evidence to show eral quick insufflations before reinitiating chest compressions.
that one waveform is superior over another with regard to Intracardiac injection of epinephrine is to be avoided.
ROSC or survival to hospital discharge. External defibrillators
are now available with biphasic waveforms.
Correction of Hypoxia
Electronic Pacemaker Hypoxia should be corrected early during CPR with admin-
istration of the highest possible oxygen concentration. Inade-
Pacemaker therapy requiring positioning of transvenous or quate perfusion, decreased pulmonary blood flow, pulmonary
transthoracic electrodes is time consuming, technically de- edema, atelectasis, and ventilationperfusion mismatch all con-
manding, and usually interferes with adequate performance tribute to the difficulty in maintaining adequate tissue oxy-
of CPR. External pacing equipment often allows myocardial genation. Inadequate tissue oxygenation results in anaerobic
capture with some discomfort and skeletal muscle contraction metabolism, the generation of lactic acid, and the development
[76]. Obviously, this is unimportant during asystole or brady- of metabolic acidosis.
cardic cardiac arrest. Unfortunately, pacing does not produce a
perfusing rhythm in most cases of cardiac arrest. Patients who
respond to emergency pacing are those with severe bradycar- Correction of Acidosis
dias or conduction block who have reasonably well-preserved
myocardial function [77]. Correction of acidosis must be considered when the arrest has
lasted for more than several minutes. Metabolic acidosis de-
velops because of tissue hypoxia and conversion to anaero-
Venous Access bic metabolism. Respiratory acidosis occurs because of apnea
or hypoventilation with intrapulmonary ventilationperfusion
Venous access with a reliable intravenous (IV) route must be abnormalities; the marked decrease in pulmonary blood flow
established early in the course of the resuscitative effort to al- that exists even with well-performed CPR also contributes.
low for the administration of necessary drugs and fluids. How- Sodium bicarbonate reacts with hydrogen ions to buffer
ever, initial defibrillation attempts and CPR should not be de- metabolic acidosis by forming carbonic acid and then carbon
layed for the placement of an IV line. Peripheral venous access dioxide and water. Each 50 mEq sodium bicarbonate gener-
through antecubital veins is often more convenient because it is ates 260 to 280 mm Hg carbon dioxide, which can be elimi-
less likely to interfere with other rescue procedures. Cannula- nated only through the expired air. Because carbon dioxide of
tion of such veins may be difficult, however, because of venous exhaled gas during CPR is decreased, the carbonic acid gener-
collapse or constriction. A large-bore catheter system should be ated by sodium bicarbonate cannot be effectively eliminated.
used because needles in the vein are apt to become dislodged Paradoxic intracellular acidosis is likely to result, and arterial
during CPR. A long catheter may be threaded into the central blood gases may not correctly reflect the state of tissue aci-
circulation. Alternatively, the extremity may be elevated for 10 dosis. The sodium and osmolar load of bicarbonate is high;
to 20 seconds and 20 mL of flush solution used to help entry excessive administration results in hyperosmolarity, hyperna-
of the drug into the central circulation [78]. Lower extremity tremia, and worsened cellular acidosis. With these concerns in
peripheral veins should be avoided because it is questionable mind, the AHA guidelines suggest that sodium bicarbonate be
whether drugs enter into the central circulation from such veins avoided until successful resuscitation has reestablished a per-
during CPR [79]. fusing rhythm [80]. In the postresuscitative state, the degree
Central venous access offers a more secure route for drug of acidosis can be better estimated from blood gases and the
administration and should be attempted if initial resuscitative acidemia corrected with hyperventilation and possibly bicar-
efforts are not successful. Femoral vein cannulation is appar- bonate administration. Sodium bicarbonate is of questionable
ently difficult to achieve during CPR, and flow into the thorax value in treating the metabolic acidosis during cardiac arrest;
is slower than with upper torso access. If the femoral vein is it has not been shown to facilitate ventricular defibrillation
successfully cannulated, a long line should be placed into the or survival in cardiac arrest [81,82]. In any case, bicarbonate
vena cava above the level of the diaphragm. Internal jugular or should not be used during cardiac arrest until at least 10 min-
subclavian routes are preferable, but central venous catheteri- utes have passed, the patient is intubated, and the patient has
zation at these sites should not be allowed to delay defibrilla- not responded to initial defibrillation and drug intervention. An
tion attempts or interfere with CPR. They should be placed by exception is the patient with known preexisting hyperkalemia
experienced operators. in whom administration of bicarbonate is recommended. The
Although central lines may be associated with an increased use of bicarbonate may also be of value in patients who have
incidence of complications for patients receiving fibrinolytic a known preexisting bicarbonate-responsive acidosis or a tri-
therapy, they are not an absolute contraindication to its use. cyclic antidepressant overdosage, or to alkalinize the urine in
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Chapter 23: Cardiopulmonary Resuscitation 195

drug overdosage. When bicarbonate is used, 1 mEq per kg citation has been noted in several studies [83], whereas ad-
may be given as the initial dose. When possible, further ther- ministration of pure -agonists (e.g., isoproterenol or dobu-
apy should be guided by the calculated base deficit. To avoid tamine) has been shown to be ineffective [84]. The -action
iatrogenically induced alkalosis, complete correction of the of epinephrine is theoretically useful in asystole and brady-
calculated base deficit should be avoided. cardic arrests by increasing heart rate. The -effect has also
been touted to convert asystole to VF or to convert fine VF
to coarse. Coarse or wide-amplitude VF is easier to convert
Volume Replacement to a perfusing rhythm than fine or small-amplitude VF. How-
ever, this may be primarily due to the shorter time course of the
Increased central volume is often required during CPR, espe- arrest in patients still manifesting wide-amplitude rather than
cially if the initial attempts at defibrillation have failed. PEA is small-amplitude VF.
particularly likely to be caused either by acute severe hypov- Epinephrine is best administered IV. As soon as possible
olemia (e.g., exsanguination) or by a cardiovascular process for after failed ventricular defibrillation attempts (or if defibrilla-
which volume expansion may be a lifesaving temporizing mea- tion is not an option), an adult in cardiac arrest should be
sure (e.g., pericardial tamponade, pulmonary embolism, and given a 1-mg dose at a 1 to 10,000 dilution (10 mL). It should
septic shock). The usual clues for hypovolemia, such as col- be given in the upper extremity or centrally (see the earlier dis-
lapsed jugular and peripheral veins and evidence of peripheral cussion in the section Venous Access), and may be repeated
vasoconstriction, are unavailable during cardiac arrest; further- every 5 minutes. If a peripheral line is used, the drug should be
more, dry mucus membranes and absence of normal secretions administered rapidly and followed by a 20-mL bolus of IV fluid
(tears and saliva) are unreliable in acute hypovolemia. Most and elevation of the extremity. It should not be administered
physical findings of tamponade, pulmonary embolism, or septic in the same IV line as an alkaline solution. If an IV line has
shock are absent during arrest. Therefore, one must be guided not been established, the endotracheal route may be used, but
by an appropriate clinical history and have a low threshold to the intracardiac route should be avoided because it is prone to
administer volume during CPR. serious complications such as intramyocardial injection, coro-
Simple crystalloids, such as 5% dextrose in water (D5 W), nary laceration, and pneumothorax. An IV infusion of 1 to
are inappropriate for rapid expansion of the circulatory blood 10 g per minute can also be given for inotropic and pressor
volume. Isotonic crystalloids (0.9% saline and Ringers lac- support. Two multicenter trials evaluating the effectiveness of
tate), colloids, or blood are necessary for satisfactory volume high-dose epinephrine in cardiac arrest failed to demonstrate
expansion. Crystalloids are more readily available, easier to ad- an improvement in survival or neurologic outcome [85,86].
minister, and less expensive than colloids. They are also free of Risks in the use of epinephrine and other -agonists include
the potential to cause allergic reactions or infections. Colloids tissue necrosis from extravasation and inactivation from ad-
are more likely to sustain intravascular volume and oncotic mixture with bicarbonate.
pressure.
If the patient has a weak pulse, simple elevation of the legs Norepinephrine
may help by promoting venous return to the central circulation.
Volume challenges should be given as needed until pulse and Norepinephrine is a potent -agonist with -activity. Its salu-
blood pressure have been restored or until there is evidence of tary -effects during CPR are similar to those of epinephrine
volume overload. [87]. However, there are no data to support the belief that it is
superior to epinephrine during an arrest.
The major effect of norepinephrine is on the blood vessels.
Initial coronary vasoconstriction usually gives way to coronary
DRUG THERAPY vasodilatation, probably as a result of increased myocardial
metabolic activity. In a heart with compromised coronary re-
Sympathomimetic Drugs and Vasopressors serve, this may cause further ischemia. During cardiac arrest, its
usefulness, like that of epinephrine, is most likely due to periph-
Sympathomimetic drugs act either directly on adrenergic re- eral vasoconstriction with an increase in perfusion pressure. In
ceptors or indirectly by releasing catecholamines from nerve patients with spontaneous circulation who are in cardiogenic
endings. Most useful during cardiac emergencies are the adren- shock (when peripheral vasoconstriction is often already ex-
ergic agents, which include the endogenous biogenic amines treme), its effect is more difficult to predict. Norepinephrine
epinephrine, norepinephrine, and dopamine, and the synthetic also causes considerable renal and mesenteric vasoconstriction,
agent isoproterenol and its derivative dobutamine [57]. Of whereas dopamine at low infusion rates causes vasodilatation
note, none of the sympathomimetics can be administered in in these vascular beds.
a line with an alkaline infusion. Extravasation of any agent Indications for the use of norepinephrine during cardiac ar-
with -adrenergic activity can result in tissue necrosis, so they rest are similar to those for epinephrine, although there does
should be infused via a central venous catheter if possible. If not appear to be any reason to prefer it to epinephrine. Nore-
extravasation does occur, 5 to 10 mg phentolamine in 10 to pinephrine appears to be most useful in the treatment of shock
15 mL saline should be infiltrated as soon as possible into the caused by inappropriate decline in peripheral vascular resis-
area of extravasation. tance, such as septic shock and neurogenic shock. It is admin-
istered by IV infusion and titrated to an adequate perfusion
pressure. Bitartrate, 4 to 8 mg (2 to 4 mg of the base), should
Epinephrine be diluted in 500 mL D5 W or 5% dextrose in normal saline.
Epinephrine is a naturally occurring catecholamine that has A typical starting infusion rate is 0.5 g per minute and most
both - and -activities. Although epinephrine is the pressor adults respond to 2 to 12 g per minute, but some require
agent used most frequently during CPR, the evidence that it rates up to 30 g per minute. Abrupt termination of the in-
improves the outcome in humans is scant. fusion (as may occur in transport) may lead to sudden severe
Indications for the use of epinephrine include all forms of hypotension.
cardiac arrest because its -vasoconstrictive activity is impor- Precautions to the use of norepinephrine include its inappro-
tant in raising the perfusion pressure of the myocardium and priate use in hypovolemic shock and in patients with already
brain. The importance of -adrenergic activity during resus- severe vasoconstriction. Intra-arterial pressure monitoring
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196 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

is strongly recommended when using norepinephrine because receptor activity dilates renal and mesenteric arterial beds at
indirect blood pressure measurement is often incorrect in pa- low doses (1 to 2 g per kg per minute). -adrenergic activity is
tients with severe vasoconstriction. In patients with myocardial more prominent with doses from 2 to 10 g per kg per minute,
ischemia or infarction, the myocardial oxygen requirements whereas -adrenergic activity is predominant at doses greater
are increased by all catecholamines, but especially by nore- than 10 g per kg per minute It has not been shown that these
pinephrine because of its marked afterload-increasing proper- dose ranges have relevance in the clinical setting. Indications
ties. Unless the increased oxygen delivery occasioned by the for the use of dopamine are primarily significant hypotension
rise in perfusion pressure outweighs the increase in myocardial and cardiogenic shock.
oxygen requirement caused by the afterload increase, nore- Dopamine is administered by IV titration in the range of
pinephrine is likely to have deleterious effects. Heart rate, 2 to 20 g per kg per minute. Rarely, a patient may need in
rhythm, ECG evidence for ischemia, direct systemic and pul- excess of 20 g per kg per minute. A 200-mg ampule is diluted
monary pressures, urine output, and cardiac output should to 250 or 500 mL in D5 W or 5% dextrose in normal saline
be closely monitored when using this drug in patients with for a concentration of 800 or 400 mg per mL. As with all
myocardial ischemia or infarction. catecholamine infusions, the lowest infusion rate that results
in satisfactory perfusion should be the goal of therapy.
Isoproterenol Precautions for dopamine are similar to those for other
catecholamines. Tachycardia or ventricular arrhythmias may
This synthetic catecholamine has almost pure -adrenergic
require reduction in dosage or discontinuation of the drug.
activity. Its cardiac activity includes potent inotropic and
If significant hypotension occurs from the dilating activity of
chronotropic effects, both of which will increase the my-
dopaminergic or -active doses, small amounts of an -active
ocardiums oxygen demand. In addition to bronchodilatation,
drug may be added. Dopamine may increase myocardial is-
the arterial beds of the skeletal muscles, kidneys, and gut di-
chemia.
late, resulting in a marked drop in systemic vascular resistance.
Cardiac output can be expected to increase markedly unless the
increased myocardial oxygen demand results in substantial my-
Dobutamine
ocardial ischemia. Systolic blood pressure is usually maintained Dobutamine is a potent synthetic -adrenergic agent that dif-
because of the rise in cardiac output, but the diastolic and mean fers from isoproterenol in that tachycardia is less problematic.
pressures usually decrease. As a result, coronary perfusion pres- Unless ischemia supervenes, cardiac output will increase, as
sure drops at the same time that the myocardial oxygen require- will renal and mesenteric blood flow.
ment is increased. This combination can be expected to have Dobutamine is indicated primarily for the short-term en-
deleterious effects in patients with ischemic heart disease, es- hancement of ventricular contractility in the patient with heart
pecially during cardiac arrest. The main clinical usefulness of failure. It may be used for stabilization of the patient after re-
isoproterenol is in its ability to stimulate pacemakers within suscitation or for the patient with heart failure refractory to
the heart. other drugs. It may also be used in combination with IV ni-
Indications for isoproterenol are primarily in the setting of troprusside, which lowers peripheral vascular resistance and
atropine-resistant, hemodynamically significant bradyarrhyth- thereby left ventricular afterload. Although nitroprusside low-
mias, including profound sinus and junctional bradycardia, ers peripheral resistance, dobutamine maintains the perfusion
as well as various forms of high-degree AV block. It should pressure by augmenting the cardiac output.
be used only as an interim measure, until effective transcuta- Dobutamine is administered by slow-titrated IV infusion.
neous or IV pacing can be instituted. If the aortic diastolic pres- A dose as low as 0.5 g per kg per minute may prove to be
sure is already low, epinephrine is likely to be better tolerated effective, but the usual dose range is 2.5 to 10.0 g per kg per
as a stimulus to pacemakers. Under no circumstances should minute. A 250-mg vial is dissolved in 10 mL of sterile water
isoproterenol be used during cardiac arrest. and then to 250 or 500 mL D5 W for a concentration of 1.0 or
Isoproterenol is administered by titration of an IV solution. 0.5 g per mL.
One mg isoproterenol (Isuprel) is diluted with either 250 mL Precautions for dobutamine are similar to those for other
D5 W (4 mg per mL) or 500 mL D5 W (2 mg per mL). The in- -agonists. Dobutamine may cause tachycardia, ventricular ar-
fusion rate should be only rapid enough to effect an adequate rhythmias, myocardial ischemia, and extension of infarction.
perfusing heart rate (2 to 20 g per minute, or 0.05 to 0.5 g It must be used with caution in patients with coronary artery
per kg per minute). Depending on the adequacy of cardiac re- disease.
serve, a target heart rate as low as 50 to 55 beats per minute
may be satisfactory. Occasionally, more rapid rates are neces- Vasopressin
sary.
Vasopressin is not a catecholamine, but a naturally occurring
Precautions in the use of isoproterenol are largely due to
antidiuretic hormone. In high doses, it is a powerful constrictor
the increase in myocardial oxygen requirement, with its po-
of smooth muscles and as such has been studied as an adjunc-
tential for provoking ischemia; this effect, coupled with the
tive therapy for cardiac arrest in an attempt to improve perfu-
possibility of dropping the coronary perfusion pressure, makes
sion pressures and organ flows. Vasopressin may be especially
isoproterenol a dangerous selection in the coronary patient.
useful in prolonged cardiac arrest as it remains effective as a
The marked chronotropic effects may cause tachycardia and
vasopressor even in severe acidosis [88]. It may be used as a
provoke serious ventricular arrhythmias, including VF. Iso-
first agent in arrest in lieu of epinephrine or as the second agent
proterenol is usually contraindicated if tachycardia is already
if the first dose of epinephrine failed to cause a return in pulse.
present, especially if the arrhythmia may be secondary to digi-
The dose of vasopressin is 40 units IV or IO.
talis toxicity. If significant hypotension develops with its use, it
may be combined with another -agonist with -activity. How-
ever, switching to dopamine or epinephrine is usually prefer-
able; better yet is the use of pacing for rate control. Antiarrhythmic Agents
Antiarrhythmic agents have been thought to play an important
Dopamine role in stabilizing the rhythm in many resuscitation situations;
This naturally occurring precursor of norepinephrine has -, -, however, the data in support of their value are scanty. Although
and dopamine-receptorstimulating activities. The dopamine- lidocaine, bretylium, and procainamide had been considered
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Chapter 23: Cardiopulmonary Resuscitation 197

useful in counteracting the tendency to ventricular arrhyth- Administration of lidocaine begins with an IV bolus. The
mias, convincing evidence of benefit to their use for pulseless onset of action is rapid. Its duration of action is brief, but may
VT and VF is wanting. On the basis of recent studies, amio- be prolonged by continuous infusion. A solution of lidocaine,
darone has gained considerable acceptance for the emergency typically 20 mg per mL (2%), should be prepared for IV ad-
treatment of refractory VT and VF. ministration. Prefilled syringes are available for bolus injection
(see the section Ventricular Fibrillation and Pulseless Ventric-
Amiodarone ular Tachycardia for current dosing recommendations). If the
patient has suffered an acute myocardial infarction and has had
Amiodarone is a benzofuran derivative that is structurally
ventricular arrhythmias, the infusion is continued for hours to
similar to thyroxine and contains a considerable level of io-
days and tapered slowly. If the cause of the arrhythmia has
dine. Gastrointestinal absorption is slow; therefore, when given
been corrected, the infusion may be tapered more rapidly.
orally, the onset of action is delayed while the drug slowly accu-
Precautions should be taken against excessive accumulation
mulates in adipose tissue. The mean elimination half-life is 64
of lidocaine. The dosage should be reduced in patients with low
days (range, 24 to 160 days). IV administration allows rapid
cardiac output, congestive failure, hepatic failure, and age older
onset of action, with therapeutic blood levels achieved with
than 70 years because of the decreased liver metabolism of
600 mg given over 24 hours.
the drug. Toxic manifestations are usually neurologic, and can
Amiodarone decreases myocardial contractility, and it also
vary from slurred speech, tinnitus, sleepiness, and dysphoria
causes vasodilatation, which counterbalances the decrease in
to localizing neurologic symptoms. Frank seizures may occur
contractility. In general, it is therefore well tolerated even by
with or without preceding neurologic symptoms and may be
those with myocardial dysfunction.
controlled with short-acting barbiturates or benzodiazepines.
Amiodarone given IV has been successful in terminating a
Conscious patients should be warned about possible symptoms
variety of reentrant and other types of supraventricular and
of neurologic toxicity and asked to report them immediately if
ventricular rhythms. In a major study of out-of-hospital car-
they occur. Enlisting the patients aid may also allay the fear that
diac arrest due to ventricular arrhythmias refractory to shock,
could otherwise develop from unexpected neurologic symp-
patients were initially treated with either amiodarone (246 pa-
toms. Excessive blood levels can significantly depress myocar-
tients) or placebo (258 patients). Patients given amiodarone
dial contractility.
had a higher incidence of bradycardia (41% vs. 25%) and hy-
potension (59% vs. 48%), but also a higher rate of survival
to hospital admission (44% vs. 34%) [89]. This study did not Procainamide
demonstrate an increase in survival to hospital discharge or in
Procainamide hydrochloride is an antiarrhythmic agent with
neurologic status. On the basis of this study, amiodarone has
quinidine-like activity. Like quinidine, it is useful in suppressing
been given status as an option for use after defibrillation at-
a wide variety of ventricular and supraventricular arrhythmias.
tempts and epinephrine in refractory ventricular arrhythmias
It is effective against reentrant as well as ectopic arrhythmo-
during cardiac arrest. It is also an option for ventricular rate
genic mechanisms. It has somewhat less vagolytic effect than
control in rapid atrial arrhythmias in patients with impaired
quinidine and does not cause the rise in digoxin level seen with
left ventricular function when digitalis has proved ineffective.
quinidine. Procainamide is sometimes of use in the critical care
Other optional uses are for control of hemodynamically stable
setting for the suppression of ventricular arrhythmias not ef-
VT, polymorphic VT, preexcited atrial arrhythmias, and wide-
fectively treated by amiodarone or lidocaine or in patients who
complex tachycardia of uncertain origin. It may also be useful
cannot be treated with either of these two agents. It may also
for chemical cardioversion of atrial fibrillation or as an adjunct
be used in patients with supraventricular arrhythmias causing
to electric cardioversion of refractory paroxysmal supraven-
hemodynamic compromise or worsening ischemia.
tricular tachycardia (PSVT) and atrial fibrillation or flutter.
Procainamide is administered either orally or by IV in-
Administration in cardiac arrest (pulseless VT or VF) is by
jection. For serious arrhythmias in the critical care setting,
rapid IV infusion of 300 mg diluted in 20 to 30 mL of saline
IV injection is preferable. An infusion of 20 mg per minute
or D5 W. Supplementary infusions of 150 mg may be used for
(0.3 mg per kg per minute) is given up to a loading dose of
recurrent or refractory VT or VF.
17 mg per kg (1.2 g for a 70-kg patient) or until the arrhyth-
Administration for rhythms with a pulse is by IV infusion
mia is suppressed, hypotension develops, or the QRS widens by
of 150 mg given during 10 minutes, followed by infusion of
50% of its original width. A maintenance infusion may then be
1 mg per minute for 6 hours and then 0.5 mg per minute.
started at 1 to 4 mg per minute. The dosage should be lowered
Supplemental infusions of 150 mg may be given for recurrent
in the presence of renal failure. Blood levels of procainamide
or resistant arrhythmias to a total maximum dose of 2 g during
and its metabolite N-acetylprocainamide should be monitored
24 hours.
in patients with renal failure or patients who are receiving more
than 3 mg per minute for more than 24 hours. Infusions as low
Lidocaine as 1.4 mg per kg per hour may be needed in patients with renal
This antiarrhythmic agent has been used for ventricular ar- insufficiency.
rhythmias, such as premature ventricular complexes and VT. Precautions in the use of procainamide include its produc-
Premature ventricular complexes are not unusual in apparently tion of systemic hypotension, disturbance in AV conduction,
healthy people and most often are benign. Even in the patient and decreased ventricular contractility. IV infusion must be
with chronic heart disease, premature ventricular complexes carefully monitored, with frequent blood pressure determina-
and nonsustained VT are usually asymptomatic, and contro- tions and measurement of ECG intervals PR, QRS, and QT. Hy-
versy exists concerning the need to treat under these circum- potension usually responds to slowing the infusion rate. If the
stances. The situation is different for patients with myocardial QRS interval increases by more than 50% of its initial width,
ischemia or recent myocardial infarction, who are much more procainamide infusion should be discontinued. Widened QRS
likely to progress from premature ventricular complexes to sus- signifies toxic blood levels and may herald serious AV con-
tained VT or VF. There is some evidence for the efficacy of duction abnormalities and asystole. This is particularly true of
prophylactic lidocaine in reducing primary VF in patients with patients with digitalis intoxication and those with antecedent
acute myocardial infarction. However, the toxic-to-therapeutic AV conduction abnormalities. A marked increase in QT inter-
ratio is not favorable enough to warrant its routine use in val may predispose a patient to torsades de pointes. Patients
patients with suspected acute myocardial infarction [90]. who have ventricular arrhythmias of the torsades variety or
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198 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

ventricular arrhythmias associated with bradycardias should Magnesium


not be treated with procainamide.
Cardiac arrhythmias and even sudden cardiac death have been
associated with magnesium deficiency [91]. Hypomagnesemia
decreases the uptake of intracellular potassium and may pre-
Adenosine cipitate VT or fibrillation. Routine use of magnesium in cardiac
Adenosine is an endogenous purine nucleoside that depresses arrest or after myocardial infarction is not recommended. Mag-
AV nodal conduction and sinoatrial nodal activity. Because of nesium may be of value for patients with torsades de pointes,
the delay in AV nodal conduction, adenosine is effective in ter- even in the absence of hypomagnesemia.
minating arrhythmias that use the AV node in a reentrant cir- Magnesium is administered IV. For rapid administration
cuit (e.g., PSVT) [91]. In supraventricular tachycardias, such during VT or VF with suspected or documented hypomagne-
as atrial flutter or atrial fibrillation, or atrial tachycardias that semia, 1 to 2 g may be diluted in 100 mL of D5 W and given
do not use the AV node in a reentrant circuit, blocking trans- during 1 to 2 minutes. A 24-hour infusion of magnesium may
mission through the AV node may prove helpful in clarifying be used for peri-infarction patients with documented hypomag-
the diagnosis [92,93]. However, the use of adenosine in wide- nesemia. A loading dose of 1 to 2 g is diluted in 100 mL D5 W
complex tachycardia of uncertain origin to discriminate be- and slowly given during 5 minutes to 1 hour, followed by an
tween VT and supraventricular tachycardia with aberrancy is infusion of 0.5 to 1 g per hour during the ensuing 24 hours.
discouraged. The half-life of adenosine is less than 5 seconds Clinical circumstances and the serum magnesium level dictate
because it is rapidly metabolized. the rate and duration of the infusion. Hypotension or asystole
Administration is by IV bolus of 6 mg given during 1 to 3 may occur with rapid administration.
seconds, followed by a 20-mL saline flush. An additional dose
of 12 mg may be given if no effect is seen within 1 to 2 minutes.
Patients taking theophylline may need higher doses.
Side effects caused by adenosine are transient and may in-
clude flushing, dyspnea, and angina-like chest pain (even in the Other Agents
absence of coronary disease). Sinus bradycardia and ventric-
Additional drugs occasionally found useful or necessary dur-
ular ectopy are common after terminating PSVT with adeno-
ing resuscitation or in the immediate postresuscitation period
sine, but the arrhythmias are typically short lived so as to be
include atropine, calcium, nitroprusside, and nitroglycerine;
clinically unimportant. The reentrant tachycardia may recur
these agents are discussed in the following sections. Many
after the effect of adenosine has dissipated and may require
other drugs may be required in particular circumstances and
additional doses of adenosine or a longer acting drug, such as
are discussed in other parts of this text. An incomplete list of
verapamil or diltiazem.
these drugs includes beta-blockers, ibutilide, propafenone, fle-
Theophylline and other methylxanthines, such as theo-
cainide, sotalol, digoxin, antibiotics, thiamine, thyroxine, mor-
bromine and caffeine, block the receptor responsible for adeno-
phine, naloxone, adrenocorticoids, fibrinolytic agents, antico-
sines electrophysiologic effect; therefore, higher doses may be
agulants, antiplatelet agents, and dextrose.
required in their presence. Dipyridamole and carbamazepine,
on the other hand, potentiate and may prolong the effect of
adenosine; therefore, other forms of therapy may be advisable.
Atropine Sulfate
Atropine is an anticholinergic drug that increases heart rate
Verapamil and Diltiazem by stimulating pacers and facilitating AV conduction that is
Unlike other calcium channelblocking agents, verapamil and suppressed by excessive vagal tone.
diltiazem increase refractoriness in the AV node and signifi- Atropine is indicated primarily in bradycardias causing
cantly slow conduction. This action may terminate reentrant hemodynamic difficulty or associated with ventricular arrhyth-
tachycardias that use the AV node in the reentrant circuit (e.g., mias (see Fig. 23.17). Atropine may be useful in AV block at the
PSVT). These drugs may also slow the ventricular response in nodal level. It is also used in asystole and bradycardic arrests
patients with atrial flutter or fibrillation and even in patients in the hope that decreased vagal tone will allow the emergence
with multifocal atrial tachycardia. They should be used only in of an effective pacemaker [57].
patients in whom the tachycardia is known to be supraventric- Atropine is administered by IV bolus. If a rapid, full
ular in origin. vagolytic response is desired, as in asystole or bradycardic ar-
Administration of verapamil is by IV bolus of 2.5 to 5.0 mg rest, 1 mg should be administered IV at once. If a satisfactory
during 2 minutes. In the absence of a response, additional doses response has not occurred within several (3 to 5) minutes, ad-
of 5 to 10 mg may be given at 15- to 30-minute intervals to a ditional 1-mg doses should be given in a bolus, to a maximum
maximum of 20 mg. The maximum cumulative dose is 20 mg. dose of 3 mg (0.04 mg per kg). For bradycardia with a pulse,
Diltiazem may be given as an initial dose of 0.25 mg per kg with the initial dose should be 0.5 mg repeated every 5 minutes until
a follow-up dose of 0.35 mg per kg, if needed. A maintenance the desired effect is obtained, to a maximum dose of 3 mg (0.04
infusion of 5 to 15 mg per hour may be used to control the rate mg per kg). Atropine may be given by the endotracheal route
of ventricular response in atrial fibrillation. at doses 2.5 times the IV dose.
Verapamil and diltiazem should be used for arrhythmias Precautions for atropine include the requirement that an
known to be supraventricular in origin and in the absence of inordinately rapid heart rate not be produced. Patients with
preexcitation. Both verapamil and diltiazem may decrease my- ischemic heart disease are likely to have worsened ischemia or
ocardial contractility and worsen congestive heart failure or ventricular arrhythmias if the rate is too rapid. Uncommonly,
even provoke cardiogenic shock in patients with significant left a patient will have a paradoxic slowing of rate with atropine;
ventricular dysfunction. They should, therefore, be used with this is more likely to occur with smaller first doses and is caused
caution in patients with known cardiac failure or suspected by a central vagal effect. This effect is rapidly counteracted by
diminished cardiac reserve and in the elderly. If worsened fail- additional atropine. In this situation, the next dose of atropine
ure or hypotension develops after the use of these agents, cal- should be given immediately. If additional atropine does not
cium should be administered, as described in the section Other correct the problem, the patient may require judicious use of
Agents. isoproterenol or pacemaker therapy.
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Chapter 23: Cardiopulmonary Resuscitation 199

Calcium to nitroprusside infusion. Nitroprusside has also become a pre-


ferred treatment for patients in hypertensive crisis.
Calciums positive inotropic effect has led to its use in car-
Nitroprusside is administered by IV infusion. The onset of
diac arrest. The contractile state of the myocardium depends
action is rapid so that the effects of dose change become appar-
in part on the intracellular concentration of the calcium ion.
ent within several minutes. For patients with severe left ventric-
Transmembrane calcium flux serves an important regulatory
ular failure, infusion should begin at 10 g per minute, with
function in both active contraction and active relaxation. The
increments of 5 to 10 g per minute at 5-minute intervals. Most
use of calcium in cardiac arrest is based on an early report by
patients respond to a total dose of 50 to 100 g per minute,
Kay and Blalock [94] in which several pediatric cardiac sur-
although an occasional patient requires a significantly higher
gical patients were successfully resuscitated, apparently with
dose. Patients in hypertensive crisis may be started at 50 g
the aid of calcium. However, several field studies have failed
per minute and may require as much as 400 to 1,000 g per
to demonstrate an improvement in survival or neurologic out-
minute. Nitroprusside is available in 50-mg vials of dihydrate.
come with the use of calcium versus a control [95]. In addition,
The drug should be dissolved in 5 mL of D5 W and diluted to a
after standard doses of calcium administered during cardiac ar-
volume of 250 to 1,000 mL in D5 W. Because of the instability
rest, many patients are found to have very high calcium blood
of the reconstituted solution, it is recommended that it be used
levels [96]. This is apparently due to the markedly contracted
within 4 hours. The solution should be wrapped in opaque ma-
volume of distribution of the ion in the arrested organism. In
terial because nitroprusside will deteriorate more rapidly with
addition, calcium has the theoretic disadvantage of facilitating
exposure to light.
postanoxic tissue damage, especially in the brain and heart.
Precautions for nitroprusside include hypotension, usually
Digitalis toxicity may be exacerbated by the administration of
secondary to excessive dosage. Although most patients with hy-
calcium.
potension cannot tolerate nitroprusside, some can be given ni-
Calcium is indicated only in those circumstances in which
troprusside with volume repletion. Nitroprusside is converted
calcium has been shown to be of benefit [57]: calcium chan-
to cyanide in the blood, which is metabolized to thiocyanate
nel blocker toxicity, severe hyperkalemia, severe hypocalcemia,
by the liver. Thiocyanate is cleared by the kidney and can ac-
arrest after multiple transfusions with citrated blood, fluoride
cumulate in renal failure. Signs and symptoms of thiocyanate
toxicity, and while coming off heartlung bypass after cardio-
toxicity (more likely in liver failure) include nausea, tinnitus,
plegic arrest.
blurred vision, and delirium; signs of cyanide toxicity include
Calcium is available as calcium chloride, calcium gluceptate,
elevated superior vena cava, or mixed venous oxygen satura-
and calcium gluconate. The gluconate salt is unstable and less
tion and a lactic acidosis. Nitroprusside should be discontinued
frequently available. The chloride salt provides the most direct
if the latter two signs are observed.
source of calcium ion and produces the most rapid effect. The
gluceptate and gluconate salts require hepatic degradation to
release the free calcium ion. Calcium chloride is, therefore, the Nitroglycerin
best choice. It is highly irritating to tissues and must be injected
Like nitroprusside, nitroglycerin is a vasodilator that may
into a large vein with precautions to avoid extravasation. Cal-
prove to be useful in the emergency treatment of the postre-
cium chloride is available in a 10% solution. An initial dose
suscitation patient. It may be given sublingually, transdermally,
of 250 to 500 mg may be administered slowly during several
or IV, depending on the situation and desired dose. Unlike ni-
minutes. It may be repeated as necessary at 10-minute intervals
troprusside, nitroglycerin is a more potent dilator of venous
if strong indications exist.
capacitance vessels than of arterioles; therefore, it is more a
Precautions for calcium use include the need for slow injec-
preload reducer than an afterload reducer. Coronary dilatation
tion without extravasation. If bicarbonate has been adminis-
does occur and may be particularly beneficial in patients with
tered through the same line, it must be cleared before introduc-
coronary spasm and acute ischemia. Myocardial ischemia is re-
ing the calcium. If the patient has a rhythm, rapid injection may
versed through the lowering of preload and myocardial oxygen
result in bradycardia. Calcium salts must be used with caution
consumption as well as by coronary dilatation.
in patients receiving digitalis.
Sublingual or transdermal nitroglycerin is indicated for
angina. The sublingual route is preferable. For persistent or
frequently recurring ischemia unrelieved by other routes of ad-
Sodium Nitroprusside ministration, an infusion of nitroglycerin is often effective. It is
This is a rapidly acting dilator of both arteries and veins. Sys- useful for suspected coronary spasm. An infusion of nitroglyc-
temic arterial dilatation decreases impedance to left ventricular erin may also be used for preload reduction in patients with left
outflow (afterload reduction), thereby diminishing resistance ventricular failure. It may be given together with an infusion of
to left ventricular ejection and improving cardiac output. Ve- nitroprusside, especially if ischemia has not been reversed by
nous dilatation simultaneously provides preload reduction by the hemodynamic effects of nitroprusside alone.
withholding blood from the central circulation and reducing Nitroglycerin is administered by a sublingual tablet or spray
left ventricular filling pressure and volume. Myocardial oxy- (0.3 to 0.4 mg) or by a transdermal patch or ointment. For rapid
gen consumption drops and subendocardial blood flow may effect, the sublingual route should be used. It may be repeated
rise as the ventricular wall stress is lowered. In addition, the every 3 to 5 minutes, if pain relief or ST-segment deviation
lowered left ventricular filling pressures cause a decrease in has not occurred. If ischemia persists, an infusion should be
pulmonary capillary pressure and pulmonary congestion. Al- started and titrated to achieve the desired result. A 50-mg bolus
though vasodilators are most commonly used in the critical of nitroglycerin may be given before the initiation of an IV
care unit, they are occasionally needed in the emergency room drip. Two 20-mg vials may be diluted in 250 mL D5 W for a
to aid in the stabilization of the resuscitated patient with severe concentration of 160 g per mL. The infusion is started at
left ventricular dysfunction. 10 to 20 mg per minute and increased by 5 to 10 g every
Nitroprusside is indicated in any situation in which cardiac 5 to 10 minutes until the desired effect is achieved (e.g., fall
output is severely reduced, causing either cardiogenic shock in left ventricular pressure to 15 to 18 mm Hg, relief of chest
with elevated systemic vascular resistance or pulmonary con- pain, or return of ST segments to baseline). Although most
gestion from elevated left ventricular filling pressure. Patients patients respond to 50 to 200 g per minute, an occasional
with aortic or mitral regurgitation or a left-to-right shunt from patient will require 500 g per minute or more; however, the
a ventricular septal rupture are apt to respond well especially maintenance of high plasma levels of nitroglycerin may induce
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200 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

tolerance. Whenever possible, intermittent dosing with nitrate- dose, attempts should be made to decrease the dose, and other
free periods is recommended, and the use of the lowest effective modalities of therapy, including heparin or cardiac catheteri-
dose is advised. zation, should be considered with a view to early revasculari-
Precautions for nitroglycerin use include hypotension and zation.
syncope, especially if the patient has had an acute myocar-
dial infarction, is volume depleted, has either restriction to
left ventricular filling (e.g., pericardial constriction or tampon-
ade, hypertrophic disease, mitral stenosis, pulmonic stenosis, or CLINICAL SETTINGS
pulmonary hypertension) or obstruction to left ventricular out-
flow (e.g., aortic stenosis, pulmonic stenosis, or hypertrophic The procedures involved in the resuscitation of a person who
obstructive cardiomyopathy). Rapid titration of IV nitroglyc- has experienced cardiovascular or respiratory collapse are all
erin in patients with left ventricular failure requires careful part of a continuum progressing from the initial recognition of
hemodynamic monitoring to ensure efficacy and safety. The the problem and the institution of CPR to intervention with
hypotensive patient may be placed in the Trendelenburg posi- defibrillators, drugs, pacemakers, transport, and postresusci-
tion and given volume replacement. Rarely, a patient with se- tative evaluation and care (Figs. 23.14 to 23.17). The follow-
vere obstructive coronary disease develops worsened ischemia ing sections focus on the pharmacologic and electric interven-
with nitroglycerin through a coronary steal mechanism. If is- tions appropriate to various clinical settings common in cardiac
chemia is persistent in spite of maximal tolerated nitroglycerin arrest.

No movement or response

2
PHONE 911 or emergency number
Get AED
or send second rescuer (if available) to do this

Open AIRWAY, check BREATHING

If not breathing, give 2 BREATHS that make chest rise

5
5A
Definite
If no response, check pulse: pulse Give 1 breath every
Do you DEFINITELY feel 5 to 6 seconds
pulse within 10 seconds? Recheck pulse every
2 minutes
No pulse
6
Give cycles of 30 COMPRESSIONS and 2 BREATHS
until AED/defibrillator arrives, ALS providers take over, or
victim starts to move
Push hard and fast (100/min) and release completely
Minimize interruptions in compressions

7
AED/defibrillator ARRIVES

Check Rhythm
Shockable rhythm?
Shockable Not Shockable
9 10
Give 1 shock Resume CPR immediately
Resume CPR immediately for 5 cycles FIGURE 23.14. Adult basic life support health
for 5 cycles Check rhythm every care provider algorithm. [From Circulation
5 cycles: continue until ALS 112[Suppl 24]:IV-1934, 2005, with permis-
providers take over or sion. Copyright 2005, American Heart Associ-
victim starts to move ation guidelines for cardiopulmonary resuscita-
tion and emergency cardiovascular care.]
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Chapter 23: Cardiopulmonary Resuscitation 201

PULSELESS ARREST
BLS algorithm: Call for help, give CPR
Give oxygen when available
Attach monitor/defibrillator when available

2
Shockable Check rhythm Not Shockable
3 Shockable rhythm? 9
VF/VT Asystole/PEA

4
Give 1 shock
Manual biphasic: device specific
10
(typically 120 to 200 J)
Note: If unknown, use 200 J Resume CPR immediately for 5 cycles
AED: device specific When IV/IO available, give vasopressor
Monophasic: 360 J Epinephrine 1 mg IV/IO
Resume CPR immediately Repeat every 3 to 5 min
or
May give 1 dose of vasopressin 40 U IV/IO to
5 Give 5 cycles of CPR*
replace first or second dose of epinephrine
Check rhythm No
Consider atropine 1 mg IV/IO
Shockable rhythm? for asystole or slow PEA rate
Repeat every 3 to 5 min (up to 3 doses)
6 Shockable

Continue CPR while defibrillator is charging


Give 1 shock Give 5 cycles
Manual biphasic: device specific of CPR*
(same as first shock or higher dose)
Note: if unknown, use 200 J 11
AED: device specific
Monophasic: 360 J Check rhythm
Resume CPR immediately after the shock Shockable rhythm?
When IV/IO available, give vasopressor during CPR
(before or after the shock)
Epinephrine 1 mg IV/IO
Repeat every 3 to 5 min
or
May give 1 dose of vasopressin 40 U IV/IO to 12
replace first or second dose of epinephrine
13
If asystole, go to Box 10 Not
If electrical activity, check Shockable Shockable Go to
Give 5 cycles of CPR* pulse. If no pulse, go to
7 Box 4
Box 10
Check rhythm No If pulse present, begin
Shockable rhythm? postresuscitation care

Shockable
8 During CPR
Continue CPR while defibrillator is charging Push hard and fast (100/min) Rotate compressors every
Give 1 shock Ensure full chest recoil 2 minutes with rhythm checks
Manual biphasic: device specific Search for and treat possible
(same as first shock or higher dose) Minimize interruptions in chest
contributing factors:
Note: If unknown, use 200 J compressions Hypovolemia
AED: device specific One cycle of CPR: 30 compressions Hypoxia
Monophasic: 360 J then 2 breaths; 5 cycles 2 min Hydrogen ion (acidosis)
Resume CPR immediately after the shock Avoid hyperventilation Hypo-/hyperkalemia
Consider antiarrhythmics; give during CPR Hypoglycemia
(before or after the shock) Secure airway and confirm placement Hypothermia
amiodarone (300 mg IV/IO once, then Toxins
consider additional 150 mg IV/IO once) or Tamponade, cardiac
lidocaine (1 to 1.5 mg/kg first dose, then 0.5 to
* After an advanced airway is placed, Tension pneumothorax
rescuers no longer deliver cycles
0.75 mg/kg IV/IO, maximum 3 doses or 3 mg/kg) of CPR. Give continous chest com- Thrombosis (coronary or
Consider magnesium, loading dose pressions without pauses for breaths. pulmonary)
1 to 2 g IV/IO for torsades de points Give 8 to 10 breaths/minute. Check Trauma
After 5 cycles of CPR,* go to Box 5 above rhythm every 2 minutes

FIGURE 23.15. Advanced cardiac life support pulseless arrest algorithm. [From Circulation 112[Suppl
24]:IV-5866, 2005, with permission. Copyright 2005, American Heart Association guidelines for car-
diopulmonary resuscitation and emergency cardiovascular care.]

arrests in the emergency room will be in monitored patients;


Ventricular Fibrillation and Pulseless the rescuer, however, must never rely solely on the monitored
Ventricular Tachycardia signal but must always confirm the need for CPR by determin-
ing the absence of a pulse. Quick-look paddles or pads should
Electric defibrillation is the most important intervention in confirm the diagnosis of VF or VT and a countershock should
treating these arrhythmias (see Chapter 6). The sooner it is be attempted (120 to 200 J for biphasic defibrillators and 360
administered, the more likely it is to succeed. If a defibrilla- J for monophasic defibrillators). CPR should be resumed with-
tor is not immediately available and an adult cardiac arrest is out rechecking the rhythm or a pulse. After 2 minutes or about
witnessed, a precordial thump is recommended by some au- 5 cycles of CPR, the rhythm should be rechecked. If VF or
thors [97]; however, no recommendation for or against its use VT is still present, another shock is applied at the same energy
is made in the recent AHA guidelines [57]. Many witnessed level. CPR is again resumed immediately, and if an IV line is
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202 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

1
TACHCARDIA
With pulses

2
Assess and support ABCs as needed
Give oxygen
Monitor ECG (identify rhythm), blood pressure, oximetry
Identify and treat reversible causes
4

Symptoms persist Perform immediate


5 3
synchronized cardioversion
Establish IV access Is patient stable? Establish IV access and give
Obtain 12-lead ECG Stable Unstable signs include altered Unstable sedation if patient
(when available) mental status, ongoing chest pain, is conscious; do not delay
or rhythm strip hypotension or other signs of shock cardioversion
Is QRS narrow (<0.12 sec)? Note: rate-related symptoms Consider expert consultation
uncommon if heart rate <150/min If pulseless arrest develops,
see Pulseless Arrest Algorithm

Wide (0.12 sec)


Narrow
6 12
NARROW QRS*: WIDE QRS*:
Is rhythm regular? Is rhythm regular?
Expert consultation
Regular Irregular advised
7 11
Attempt vagal maneuvers Irregular narrow-complex Regular Irregular
Give adenosine 6 mg rapid tachycardia
13 14
IV push. If no conversion, Probable atrial fibrillation or
give 12 mg rapid IV push; possible atrial flutter or MAT If ventricular If atrial fibrillation with
may repeat 12 mg dose once (multifocal atrial tachycardia) tachycardia or aberrancy
Consider expert consultation uncertain rhythm See Irregular narrow-
8 Control rate (eg, diltiazem, Amiodarone Complex Tachycardia
Beta-blockers; use Beta-blockers 150 mg IV over 10 min (Box 11)
Does rhythm with caution in pulmonary disease Repeat as needed
convert? or CHF) to maximum dose of If pre-excited atrial
Note: consider 2.2 g/24 hours fibrillation (AF + WPW)
expert consultation Prepare for elective Expert consultation
synchronized advised
Converts Does not converts cardioversion Avoid AV nodal
blocking agents (eg,
9 10 If SVT with aberrancy adenosine, digoxin,
Give adenosine diltiazem, verapamil)
If rhythm converts, If rhythm does NOT convert,
(go to Box 7) Consider antiarrhyth-
probable reentry SVT possible atrial flutter,
(reentry supraventricular ectopic atrial tachycardia, mics (eg, amiodarone
tachycardia): or junctional tachycardia: 150 mg IV over 10 min)
Observe for recurrence Control rate (eg, diltiazem, If recurrent polymor-
Treat recurrence with Beta-blockers; use Beta-blockers phic VT, seek expert
adenosine or longer- with caution in pulmonary consultation
acting AV nodal blocking disease or CHF) If torsades de pointes,
agents (e.g., diltiazem, Treat underlying cause give magnesium
Beta-blockers) Consider expert consultation (load with 12 g over
560 min, then infusion)

During evaluation Treat contributing factors:


Secure, verify airway Hypovolemia Toxins
*Note: if patient becomes and vascular access Hypoxia Tamponade, cardiac
unstable, go to Box 4 when possible Hydrogen ion (acidosis) Tension pneumothorax
Consider expert Hypo-/hyperkalemia Thrombosis (coronary or
consultation Hypoglycemia pulmonary)
Prepare for Hypothermia Trauma (hypovolemia)
cardioversion

FIGURE 23.16. Advanced cardiac life support tachycardia algorithm. [From Circulation 112[Suppl
24]:IV-6777, 2005, with permission. Copyright 2005, American Heart Association guidelines for car-
diopulmonary resuscitation and emergency cardiovascular care.]

available, vasopressors (epinephrine, 1 mg IV, or IO every 3 additional dose of 150 mg IV/IO if necessary) or lidocaine (1.0
to 5 minutes, or vasopressin 40 units, IV/IO) are administered. to 1.5 mg per kg IV/IO followed by additional doses of 0.5 to
After another 5 cycles of CPR, the rhythm is checked again. If 0.75 mg per kg, if necessary, up to a total dose of 3 mg per kg).
VF or VT is still present, another shock is applied. Adequacy of ventilation should be assessed with an arterial
After the second shock, if the patient remains in VF or VT, blood gas determination, if possible. Sodium bicarbonate is of
consideration should be given to the administration of an an- questionable value during cardiac arrest but should be adminis-
tiarrhythmic agent: amiodarone (300 mg IV/IO once with an tered if the patient is known to have preexisting hyperkalemia.
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Chapter 23: Cardiopulmonary Resuscitation 203

BRADYCARDIA
Heart rate <60 bpm and
inadequate for clinical condition
2

Maintain patent airway; assist breathing as needed


Give oxygen
Monitor ECG (identify rhythm), blood pressure, oximetry
Establish IV access

Signs or symptoms of poor perfusion caused by the bradycardia?


(e.g., acute altered mental status, ongoing chest pain, hypotension or other signs of shock)

4A Adequate Poor 4
perfusion perfusion
Observe/Monitor Prepare for transcutaneous pacing;
use without delay for high-degree block
(type II second-degree block or
third-degree AV block)
Consider atropine 0.5 mg IV while
awaiting pacer. May repeat to a
total dose of 3 mg. If ineffective,
begin pacing
Consider epinephrine (2 to 10 g/min)
Reminders
or dopamine (2 to 10 g/kg per minute)
If pulseless arrest develops, go to Pulseless Arrest Algorithm infusion while awaiting pacer or if
Search for and treat possible contributing factors: pacing ineffective
Hypovolemia Toxins
Hypoxia Tamponade, cardiac 5
Hydrogen ion (acidosis) Tension pneumothorax
Hypo-/hyperkalemia Thrombosis (coronary or pulmonary) Prepare for transvenous pacing
Hypoglycemia Trauma (hypovolemia, increased ICP) Treat contributing causes
Hypothermia Consider expert consultation

FIGURE 23.17. Bradycardia algorithm. [From Circulation 112[Suppl 24]:I-V-6777, 2005, with per-
mission. Copyright 2005, American Heart Association guidelines for cardiopulmonary resuscitation and
emergency cardiovascular care.]

dose of epinephrine) is administered. Atropine at a dose of


Asystole 1 mg IV/IO may also be considered. After 5 cycles of CPR, the
rhythm is rechecked. If asystole persists, the aforementioned
Asystole is obviously the end result of any pulseless rhythm. sequence is repeated.
When asystole is the presenting rhythm, it is often the termina- It has been demonstrated that VF may masquerade as asys-
tion of untreated VF. In the prehospital setting, many cases of tole in several leads and for minutes at a time [98]. It is therefore
asystole are related to delayed initiation of BLS or ACLS. Pri- important to check at least two different lead configurations at
mary asystole associated with increased parasympathetic tone 90-degree orientation to confirm the diagnosis of asystole. Rou-
is less common, but does occur. Whether this rhythm occurs tine shocking of asystole, however, is discouraged because of
as the initial rhythm or follows on VT or fibrillation, it car- the possibility of increasing parasympathetic tone and thus de-
ries a very poor prognosis. Less than 1% to 2% of patients creasing further any chance of return of spontaneous rhythm.
can be expected to revert successfully to a perfusing rhythm. No improvement in survival has been demonstrated with the
Even more rarely will such patients leave the hospital with rea- use of shocks for presumed asystole [99].
sonable neurologic integrity or significant long-term survival; As in other forms of arrest, neither sodium bicarbonate nor
their best hope lies in the early discovery and treatment of calcium has been shown to be of benefit; these agents should
a reversible cause for cardiovascular collapse, such as hypo- be considered only under specific circumstances (see previous
volemia. Occasionally, asystole develops due to excessive va- discussion).
gal tone, such as is seen with induction of anesthesia, during Temporary artificial pacing is of no likely benefit in
surgical procedures, or with stimulation of the carotid body, asystoleeither primary or that following countershock. Pac-
bladder, biliary, or gastrointestinal tract. Unfortunately, most ing with endocardial, percutaneous transthoracic, or external
patients with asystole have severe coronary artery disease and transcutaneous electrodes has led to pitifully few long-term sur-
are unlikely to be saved. vivals in these cases.
In patients with apparent asystole, CPR is initiated and an The use of isoproterenol in an attempt to stimulate pace-
IV line is established as soon as possible (Fig. 23.15). Either makers through its -adrenergic agonist effects has not proved
epinephrine (1 mg IV/IO and repeated every 3 to 5 minutes) or to be beneficial. Indeed, its peripheral -stimulation produces
vasopressin (1 dose of 40 U IV/IO to replace the first or second a decrease in arterial resistance and perfusion pressure that is
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204 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

likely to be detrimental, whereas -agonists seem to increase exists of irreversible death, such as putrefaction or dependent
myocardial and cerebral perfusion. rubor.
Hypothermia may occur with environmental exposures
other than cold-water drowning. The bodys ability to main-
Pulseless Electric Activity tain temperature is diminished by alcohol, sedation, antidepres-
sants, neurologic problems, and advanced age. Because of the
PEA is present when an arrest patient is found to have orga- associated bradycardia and oxygen-sparing effects, prolonged
nized ECG ventricular complexes (QRS) not associated with hypothermia and arrest may be tolerated with complete recov-
a palpable pulse (Fig. 23.15). Pulseless VT is not considered ery. A longer period may be needed to establish breathlessness
a form of PEA. Electromechanical dissociation is a form of and pulselessness because of profound bradycardia and slowed
PEA in which the QRS is unaccompanied by any evidence respiratory rate. Resuscitative efforts should not be abandoned
of ventricular contraction and the emergency response is the until near-normal temperature has been reestablished.
same. Bradyasystolic rhythms and severe wide-complex brady- Electric shock and lightning strike may lead to tetanic spasm
cardias may be considered along with PEA. These arrhythmias of respiratory muscles or convulsion, causing respiratory ar-
may be associated with specific clinical states that if reversed rest. VF or asystole may occur from the electric shock or after
early, may lead to the return of a pulse. It is, therefore, best to prolonged respiratory arrest. Before initiating assessment and
consider them together. When PEA is encountered, severe hy- CPR, the potential rescuer must ascertain whether the person
povolemia, hypoxia, acidosis, hyperkalemia or hypokalemia, who has been shocked is still in contact with the electric en-
hypoglycemia, hypothermia, drug overdose, cardiac tampon- ergy and that live wires are not in dangerous proximity. If the
ade, massive pulmonary embolism, tension pneumothorax, individual is located at the top of a utility pole, CPR is best
and severe myocardial contractile dysfunction should be instituted after the person is lowered to the ground [101].
considered. Open-chest CPR with thoracotomy should be applied early
With the diagnosis of PEA, CPR is initiated and, as soon in cases of penetrating chest trauma associated with cardiac
as possible, volume is administered in the form of IV crys- arrest (see previous discussion). In such patients, thoracotomy
talloid or colloid. If PEA is indeed caused by intravascular by trained personnel allows for the relief of pericardial tam-
volume depletion, a fluid challenge may return a pulse. As ponade and possible control of exsanguinating hemorrhage.
described in the section Asystole, vasopressors should be Well-equipped trauma centers should have multidisciplinary
administered every 3 to 5 minutes if a pulse has not returned. teams that can provide early, definitive surgical treatment. The
In bradycardic PEA, atropine is given as in asystole. Bicarbon- unanswered question is whether another subgroup of patients
ate is used for preexisting hyperkalemia and is acceptable for who have not responded to conventional ACLS techniques (in-
known preexisting bicarbonate-responsive acidosis, tricyclic cluding defibrillation attempts and drugs) would benefit from
overdose, to alkalinize the urine with other drug overdoses and thoracotomy and open-chest CPR. Animal studies suggest that
in intubated and well-ventilated patients with prolonged arrest survival may be improved over closed-chest compression if
intervals. open-chest CPR is used within the first 15 minutes of arrest
In patients at high risk for pericardial effusions (i.e., pa- [102]. If open-chest CPR is delayed until 20 minutes or more
tients hospitalized with known malignancy, severe renal fail- of closed-chest CPR, there is no improvement in outcome de-
ure, recent myocardial infarction, or recent cardiac catheter- spite improved hemodynamics. In patients with out-of-hospital
ization), pericardiocentesis should be attempted early in the arrest in whom open-chest CPR was attempted after 30 min-
course of CPR if the patient is not responding to volume ad- utes of conventional CPR, survival did not improve [103].
ministration and -agonists. In prehospital arrests, pericardial Open-chest CPR may also be indicated in blunt trauma
tamponade is rare, but an attempt at pericardiocentesis is war- with cardiac arrest and cardiac arrest due to hypothermia, pul-
ranted if there is no favorable response to volume or -agonists. monary embolism, pericardial tamponade, or abdominal hem-
Echocardiography, when available, almost always confirms or orrhage in which initiation of conventional therapy and closed-
excludes the possibility of tamponade and may be useful in chest CPR is not proving effective. In the aforementioned cases,
delineating the volume status as well as the function of the the decision to use open-chest CPR presupposes quick avail-
ventricles. ability of definitive surgical intervention. Early surgical explo-
ration is indicated in penetrating abdominal trauma with de-
terioration and cardiac arrest in which aortic cross-clamping
Special Situations may provide temporary control of abdominal hemorrhage.
Induced therapeutic hypothermia (32 C to 34 C) for 12
Patients who have nearly drowned in cold water may recover to 24 hours improves survival and neurologic outcome in co-
after prolonged periods of submersion. Apparently, the hy- matose patients who have survived an out-of-hospital VF arrest
pothermia and bradycardia of the diving reflex may serve to [104,105]. Hypothermia may also be beneficial for in-hospital
protect against organ damage [100]. Successful resuscitation arrests. Lower cardiac index and hyperglycemia tend to occur
has been described after considerable periods of submersion more frequently in hypothermic patients. Shivering must be
[100]. Because it is often difficult for bystanders and rescuers prevented to reduce metabolic rate. Please see Chapter 64 on
to estimate the duration of submersion, in most cases it is war- hypothermia for an in-depth discussion of induced therapeutic
ranted to initiate CPR at the scene, unless physical evidence hypothermia.

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P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Med 341:871, 1999. 346:557, 2000.

CHAPTER 24 MANAGEMENT OF PAIN IN


THE CRITICALLY ILL PATIENT
ARMAGAN DAGAL, MARIO DE PINTO AND W. THOMAS EDWARDS

Pain in critically ill patients should be systematically observed ately in critically ill patients. It is estimated that as many as 70%
and regularly assessed. All means of analgesic interventions of patients experience moderate-intensity procedure-related or
should be evaluated in a coordinated, individualized, and goal- postoperative pain during their stay in the hospital intensive
oriented interdisciplinary manner. care unit (ICU) [69]. Pain is frequently treated inappropri-
Pain may stem from acute medical or surgical illness as ately because of fears of depressing spontaneous ventilation,
well as preexisting medical conditions. Mechanical ventilation, inducing opioid dependence, and precipitating cardiovascular
placement of indwelling tubes and catheters, procedures per- instability. Moreover, many clinicians often poorly understand
formed such as placement of chest tubes, intracranial pressure the methods for assessing pain, the techniques for optimally
(ICP) monitors, and turning and suctioning are also causes of treating it, and the benefits of its effective management. State-
pain [1,2]. Exposure to high levels of pain has negative psy- of-the-art pain management means not only decreasing pain
chologic and physiologic consequences, and its effective man- intensity, but also reducing analgesics side effects, which may
agement is important in the maintenance of patients dignity indeed facilitate patient recovery and is likely to shorten ICU
[35]. and hospital stay [1012]. Recent studies also suggest that ef-
Despite numerous improvement initiatives over the past two fective acute pain management may help in reducing the devel-
decades, pain is very common and often not treated appropri- opment of chronic pain [13].
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 24: Management of Pain in the Critically Ill Patient 207

In 2005, the American Pain Society (APS) published the fol- who feels happy because he or she has no pain or sad because
lowing guidelines for quality improvement in acute and cancer he or she has some or a lot of pain. The patient is then asked
pain management [14]: to choose the face that best describes how they feel from six

possible options.
Recognize, identify, and treat pain promptly.

It has been shown that the NRSs have the least variance and
Involve patients and families in the pain management plan.

may be the preferred tool overall. Mechanically ventilated and
Improve treatment patterns.

sedated patients will be unable to use the VAS ruler or other self-
Reassess and adjust the pain management plan as needed.

report pain assessment tools. Once sedation has ceased, some
Monitor processes and outcomes of pain management.
patients may be alert enough to use a VAS ruler. This should
The primary goal of this structured approach to pain man- be attempted as an option for these patients. If psychomotor
agement was to prevent pain through the administration of abilities are impaired at this point, an NRS or FPS may prove
analgesics at regular intervals and before performing poten- to be more helpful.
tially painful procedures.
Implementation of the APS guidelines in 120 postcardiac
surgery patients over a 3-month period revealed that 95% of Objective Pain Assessment
them had effective pain relief during every ICU staff shift for the
first 6 days after surgery [15]. Data also revealed dramatically When the patient is critically ill, sedated, and/or ventilated, pain
improved side-effect profile and reduced length of hospital stay. severity can be estimated only by observing the behavioral and
Implementation of a similar pain management protocol in a physiologic responses to pain:
medical ICU resulted in a decrease in ventilator days (from 10.3 The Behavioral Pain Scale (BPS) is the earliest and most
to 8.9) and significant reductions of average hospital costs.
widely tested pain assessment tool for sedated patients. The
ICU pain management strategies may also incorporate the
BPS was developed by Payen et al. There are three compo-
application of regional analgesia techniques (neuraxial and pe-
nent domains: facial expression, upper limb movement,
ripheral nerve blocks) when possible. Regional analgesia, when
and compliance with ventilation. Patients are scored from
used appropriately, helps reduce the total amount of opioid
1 to 4 on each section, giving a total score between 3 (no
analgesics necessary to achieve adequate pain control and the
pain) and 12 (maximum pain) [17].
development of potentially dangerous side effects. The Critical Care Pain Observation Tool (CPOT) was de-
signed by Gelinas et al. The CPOT has four domains: fa-
cial expression, body movement, muscle tension, and
EVALUATION OF PAIN compliance with ventilation. Patients are scored in each
section between 0 and 2, giving an overall score of 0 (no
It is difficult to perform assessment of pain in the ICU. Struc-
pain) to 8 (maximum pain).
tured approaches to pain assessment are mandatory for favor- The Non-Verbal Pain Scale (NVPS) was developed by
able patient outcome.
Odhner et al. The NVPS incorporates three behavioral do-
Pain assessment tools are useful to monitor for deterioration
mains and two physiologic domains. The behavioral do-
or improvements over time, and evaluate and titrate analgesic
mains are face, activity (movement), and guarding.
therapy appropriately [5,16].
The first physiologic domain considers vital signs and the
There are several newly proposed methods available for
second incorporates other physiologic indicators includ-
pain assessment in the ICU. The chosen strategy should be
ing skin color and temperature, perspiration, and pupillary
adapted to the patients capacity to interact with the practi-
changes. Again, specific descriptors are given to enable the
tioner in order to provide assessment of static (rest) and dy-
assessors to rate a patients pain from 0 to 2 within each
namic pain (while moving the affected part or while taking
domain, giving a total pain score between 0 (no pain) and
deep breaths or coughing).
10 (maximum pain).
Assessment of pain should include determining cause, type,
intensity, duration, site, and prior response to therapy. Catego- None of these tools can be regarded as gold standard and
rization of pain into somatic, visceral, neuropathic in nature, they require further evaluation and research to investigate the
or identification of specific sites, such as focal bone pain as impact of their use on pain management in clinical practice.
opposed to allodynia or diffuse bowel distention, is important Nonetheless, they offer a consistent and systematic approach
because it helps in determining the most effective type of inter- that might improve pain management in ICUs.
vention. Analgesic trials can be another assessment tool if pain is
In general, appropriate assessment of pain improves the suspected in ICU patients. They involve administration of a low
overall quality of pain management. dose of an analgesic followed by observation of the patients
pain-related behavior [5,18].

Subjective Pain Assessment


FORMULATION OF A
The Visual Analog Scale (VAS) is a 10-cm horizontal line, an-
chored by textual descriptors and/or pictures at each end. An TREATMENT PLAN
end-point descriptor such as no pain (a score of 0) is marked
It is important to understand the characteristics of the patho-
at the left end and worst pain imaginable (a score of 10) is
logic process responsible for pain in order to establish the most
marked at the right end.
effective therapy.
The Numerical Rating Scale (NRS) is a horizontal line with
a scale from 0 to 10. Patients are asked to choose a number that
relates to their pain intensity, where 0 represents no pain and
10 the worst imaginable pain. The NRS can be administered Character and Site
verbally or visually.
Pain can be categorized as follows:
The Faces Pain Scale (FPS) was first developed by Wong
and Baker and is recommended for those aged 3 and older. An Nociceptive pain: It occurs in response to a noxious stimulus
explanation is given to the patient that each face is a person and continues only in the presence of a persistent noxious
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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208 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

stimulus. It is transmitted through nonmyelinated C-sensory Hyperalgesia (the lowering of pain threshold and an in-
fibers and small myelinated A-fibers via the dorsal root gan- creased response to noxious stimuli), allodynia (the evocation
glion and spinothalamic pathways in the spinal cord to the of pain by non-noxious stimuli), hyperpathia (explosive pains
thalamus, periaqueductal gray, and other centers in the brain evoked in areas with an increased sensory threshold when the
[19]. Nociceptive pain is often dull, aching, sharp, or tender. stimulus exceeds the threshold), dysesthesia (spontaneous or
Somatic pain: It is due to nociceptive signals arising from evoked unpleasant abnormal sensation), and paresthesia (spon-
the musculoskeletal system. taneous or evoked abnormal sensation) are typical elements of
Visceral pain: It is due to a disease process or abnormal func- neuropathic pain.
tion of an internal organ or its covering (parietal pleura,
pericardium, and peritoneum). It can be frequently associ-
ated with nausea, vomiting, sweating, and changes in heart MEDICAL MANAGEMENT
rate and blood pressure.
Inflammatory pain occurs in response to tissue injury and Consequences of inadequate sedation and analgesia in the ICU
the subsequent inflammatory reaction. In order to help heal- may result in excessive pain and anxiety, agitation, self-removal
ing of the injured body part, the sensory nervous system un- of tubes and catheters, violence toward caregivers, myocar-
dergoes a profound change as a result; normally innocuous dial ischemia, patient-ventilator asynchrony, hypoxemia, and
stimuli now produce pain, and responses to noxious stimuli pain-related immunosuppression. In contrast, excessive and/or
are both exaggerated and prolonged [20]. This is secondary prolonged sedation can lead to skin breakdown, nerve com-
to plasticity in nociceptors and central nociceptive pathways pression, delirium, unnecessary testing for altered mental sta-
[21,22]. Ablation of a specific set of nociceptor neurons, tus, prolonged mechanical ventilation and associated problems
such as the one expressing the tetrodotoxin-resistant sodium such as ventilator-associated pneumonia (VAP), and perhaps
channel Nav1.8, eliminates inflammatory pain, but leaves post-traumatic stress disorder (PTSD). Balanced treatment us-
neuropathic pain intact, indicating a fundamental difference ing both nonpharmacologic and pharmacologic methods are
in the neuronal pathways responsible for these pain states imperative for pain management in the ICU [27,28]. Improve-
[23,24]. ment in quality of care results in a reduction of the time spent
Neuropathic pain: It can be burning, tingling, or electric on mechanical ventilation and length of stay in the ICU.
in character. Patients with neuropathic pain may describe
positive or negative neurologic phenomena. Positive phe-
nomena include spontaneous pain (arising without stimulus) Nonpharmacologic Treatments
and evoked pains (abnormal response to stimulus). Negative
phenomena include impaired sensation to touch or thermal Nonpharmacologic interventions are easy to provide, safe, and
stimuli. Neuropathic pain is initiated or caused by a primary economical. They may include attention to proper positioning
lesion or dysfunction in the central or peripheral nervous of patients to avoid pressure points, stabilization of fractures,
system (CNS or PNS). and elimination of irritating physical stimulation (e.g., avoiding
traction on the endotracheal tube).
Central neuropathic pain most commonly results from Several mechanisms have been proposed to explain how
spinal cord injury, stroke, or multiple sclerosis [25]. to inhibit or modulate the ascending transmission of a nox-
Peripheral neuropathic pain can be caused by [26] the fol- ious stimulus from the periphery or, conversely, to stimulate
lowing: descending inhibitory control from the brain [29].
Trauma (e.g., complex regional pain syndrome (CRPS) and They include the following:
chronic postsurgical pain) 1. Gate control theory
Infection (e.g., postherpetic neuralgia and HIV-induced neu- 2. Busy-line effect
ropathy) 3. Production of endogenous opioids at the periaqueductal
Ischemia (e.g., diabetic neuropathy and central poststroke gray, reticular activating system, and spinal gate
pain) 4. Activation of monoaminergic neurons in the thalamus, hy-
Cancer (e.g., invasion and compression of peripheral nerve pothalamus, and brain stem
structures) 5. Activation of second-order neurons in the dorsal horn, se-
Chemically induced (e.g., chemotherapy-induced neuropa- lective inhibition of abnormally hypersensitive neurons in
thy) the dorsal horn, and increased release of -aminobutyric
acid (GABA) in spinal neurons
Neural damage to either the PNS or the CNS provokes mal-
6. Descending inhibition from supraspinal centers via the pre-
adaptive responses in nociceptive pathways that drive sponta-
tectal zone and posterior columns
neous pain and sensory amplification. This maladaptive plas-
ticity leads to persistent changes and, therefore, needs to be Stimulation-produced analgesia (SPA) is a term that de-
considered a disease state of the nervous system in its own right, scribes noninvasive or minimally invasive techniques such as
independent of the etiologic factor(s) that triggered it. Studies acupuncture, electroacupuncture (EA), transcutaneous electric
suggest that peripheral and central sensitization mechanisms nerve stimulation (TENS), acupressure and spinal cord stim-
are also involved. In the PNS, they include altered gene expres- ulation (SCS), peripheral nerve stimulation (PNS), deep-brain
sion and changes in ion channels that lead to ectopic activity. stimulation, and motor cortex stimulation. Evidence suggests
In the CNS, the regulation of many genes also changes. In addi- that these modalities are useful as a sole or supplementary anal-
tion, synaptic facilitation and loss of inhibition at multiple lev- gesic technique for both acute and chronic painful conditions
els of the neuraxis produce central amplification. Neuronal cell [29].
death and aberrant synaptic connectivity provide the structural Peripherally applied heat causes local vasodilation that pro-
basis for persistently altered processing of both nociceptive and motes circulatory removal of biomediators of pain from the
innocuous afferent input. Highly organized neuroimmunologic site of injury, whereas cold application decreases the release of
interactions as a result of neural damage play an important part pain-inducing chemicals [30].
in the development of persistent neuropathic pain. Genetically Modifications of the ICU environment, such as creat-
determined susceptibility is also likely to unveil the risk of de- ing units with single rooms, decreasing noise, and providing
veloping neuropathic pain [24]. music and appropriate lighting that better reflect a daynight
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Chapter 24: Management of Pain in the Critically Ill Patient 209

orientation [31], may help patients achieve normal sleep pat- able, the clinician must carefully judge the risks and benefits
terns and also improve pain control. For the cognitively intact on an individual basis.
ICU patients, provision of sensory and procedural information
may improve their ability to cope with the discomfort.
Acetaminophen
Acetaminophen is an analgesic and antipyretic. It may also
Pharmacologic Treatments have anti-inflammatory properties. The mechanism of action
of acetaminophen remains unknown. The greater sensitivity of
The pharmacologic characteristics of the ideal analgesic med- cells containing COX-3 to acetaminophen is frequently cited
ication include easy titration, rapid onset and offset of action as indicating that the target of action of acetaminophen is
without accumulation, and no side effects. COX-3. Recent research indicates that acetaminophen inhibits
prostaglandin synthesis in cells that have a low rate of synthe-
sis and low levels of peroxide. When the levels of arachidonic
Nonsteroidal Anti-Inflammatory Drugs acid are low, acetaminophen appears to be a selective COX-2
Cyclooxygenase (COX) is located in all cells. It metabolizes inhibitor. Acetaminophen has predominant effects on the CNS
arachidonic acid to generate prostaglandin H2 . A number of because the peroxide and arachidonic acid levels in the brain
enzymes further modify this product to generate bioactive are lower than at peripheral sites of inflammation [38]. It is
lipids (prostanoids) such as prostacyclin, thromboxane A2 , and available in oral, rectal, and parenteral formulations. The par-
prostaglandins D2 , E2 , and F2 . Three isoforms COX-1, COX- enteral formulation is not yet available in the United Sates al-
2, and COX-3 have been described. COX-1 is ubiquitous and though approval of the Food and Drug Administration (FDA)
constitutive. COX-2 is present in areas of inflammation and is pending. Acetaminophen is an effective adjuvant to opioid
located in inflammatory cells. COX-3 is a splice variant, found analgesia, and a reduction in opioid requirement by 20% to
centrally, and its inhibition is thought to be responsible for the 30% can be achieved when combined with a regular regimen
action of acetaminophen [32]. of oral or rectal acetaminophen.
It is now recognized that COX-2 is expressed in normal en- It has been shown that 1 g of acetaminophen significantly
dothelial cells in response to shear stress and its inhibition is as- reduces postoperative morphine consumption over a 6-hour
sociated with suppression of prostacyclin synthesis. Inhibition period. Doses greater than 1,000 mg have been reported to
of COX-2 results in prothrombotic inclination on endothelial have a superior effect when compared to lower doses. IV ac-
surfaces and an increase in sodium and water retention, leading etaminophen has been shown to reduce PCA morphine require-
to edema, as well as exacerbations of heart failure and hyper- ments after spinal surgery [39] and hip arthroplasty.
tension. Loss of the protective effects of COX-2 upregulation Its side-effect profile is comparable to placebo [40];
in the setting of myocardial ischemia and infarction leads to a hypersensitivity reactions are rare. Major concerns with
larger infarct size, greater thinning of the left ventricular wall acetaminophen administration relate to the potential for hep-
in the infarct zone, and an increased tendency to myocardial atotoxicity, which, however, is extremely rare following ther-
rupture [33,34]. apeutic dosing [41]. In patients with severe liver disease, the
Blockade of the proinflammatory mediators by nonsteroidal elimination half-life can be prolonged. A reduced dose of 1 g
anti-inflammatory drugs (NSAIDs) reduces the inflammatory three times a day with short duration of therapy is recom-
response (and subsequent pain). Classically, their effect is anti- mended. Prospective studies administering acetaminophen to
inflammatory, analgesic, and antipyretic because of the di- patients consuming alcohol have found no increased evidence
rect inhibition of prostaglandin production. Adding NSAIDs of liver injury [42]. In a recent study, nonallergic hypotension
to intravenous (IV) opioid-based patient-controlled analgesia has been reported in a cohort of ICU patients on therapeutic
(PCA) reduces opioid consumption by 30% to 50% and results doses of acetaminophen. The authors indicated brain injury
in a significant reduction in the incidence of nausea, vomiting, and sepsis as the potential risk factors for this type of hypoten-
and sedation [35]. sive reaction [43].
On the other hand, the nonspecific blockade of COX in-
hibits the physiologic role of COX-1 and results in clinically
Opioids
significant deterioration of renal function and risk of devel-
opment of peptic ulceration and upper gastrointestinal (GI) For the critically ill patient, opioids remain the main pharmaco-
hemorrhage, bronchospasm, and platelet dysfunction. A meta- logic method for the treatment of pain. Despite their extensive
analysis published in 2002 showed that the risk of GI hemor- side-effect profile, there are no therapeutic alternatives avail-
rhage is related to the patient and drug-related factors, and is able currently (Table 24.1).
irrespective of the type of NSAID used. Patients who smoke, Opiates refer to the nonpeptide synthetic morphine-like
those with history of GI hemorrhage, and those taking antico- drugs while the term opioid is more generic, encompassing all
agulants are at increased risk [36]. substances that produce morphine-like actions. Opioids can be
Current evidence indicates that selective COX-2 inhibitors loosely divided into four groups:
have important adverse cardiovascular effects that include in-
creased risk for myocardial infarction, stroke, heart failure, Naturally occurring, endogenously produced opioid pep-
and hypertension. The risk for these adverse effects is likely tides (e.g., dynorphin and Met-enkephalin)
to be greatest in patients with a history of or at high risk for Opium alkaloids, such as morphine, purified from the poppy
cardiovascular disease. In these patients, COX-2 inhibitors for (Papaver somniferum)
pain relief should be used only if there are no alternatives and Semisynthetic opioids (modifications to the natural mor-
then only in the lowest dose and shortest duration necessary phine structure) such as diacetylmorphine (heroin), hydro-
[37]. Currently, celecoxib is available for clinical use world- morphone, oxycodone, and oxymorphone
wide, whereas parecoxib is available only outside the United Synthetic derivatives with structure unrelated to morphine,
States. which include the phenylpiperidine series (e.g., pethidine
Opioid-sparing properties of NSAIDs have not been stud- and fentanyl), methadone series (e.g., methadone and dex-
ied in critically ill patients, so it is unclear if potential benefits tropropoxyphene), benzomorphan series (e.g., pentazocine),
outweigh potential risks such as GI bleeding or renal failure. and semisynthetic thebaine derivatives (e.g., etorphine and
Therefore, until more evidence for such agents becomes avail- buprenorphine)
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210 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

TA B L E 2 4 . 1
GUIDELINES FOR FRONT-LOADING INTRAVENOUS ANALGESIA

Drug Total front-load dose Increments Cautions

Morphine 0.080.12 mg/kg 0.03 mg/kg q 10 min Bradycardia/hypotension (histamine)


Nausea/vomiting
Biliary colic
Acute/chronic renal failure
Elderly
Bronchospasm
Methadone 0.080.12 mg/kg 0.03 mg/kg q 15 min Accumulation/sedation
Elderly
Hydromorphone 0.02 mg/kg 2550 g/kg q 10 min Same as morphine
Dosing errors
Fentanyl 13 g/kg 0.52.00 g/kg/h Accumulation/sedation
Elderly skeletal muscle rigidity
Remifentanil 0.251.00 g/kg 0.052.00 g/kg/min Bradycardia/hypotension
Pain on discontinuation
Skeletal muscle rigidity
Ketamine 0.20.5 mg/kg 0.52.0 mg/kg/h Delirium
Increased ICP
High myocardial O2 requirement
Hypotension
Decreased CO

CO, cardiac output; ICP, intracranial pressure; q, every.

Snyder et al. in 1973 reported on the presence of specific is 5 to 10 mg and the approximate half-life is 3 hours. How-
binding sites for opioids, providing the first evidence of dis- ever, with repeated dosing or continuous infusions, half-life ki-
tinct receptors for opioids. There are several types of opioid netics become unreliable. Morphine is conjugated by the liver
receptors. They differ in their potency, selective antagonism, to metabolites that include morphine-6-glucuronide, a potent
and stereospecificity of opiate action. With a recent addition, metabolite with 20 times the activity of morphine. Both mor-
the opioid receptor subtypes are listed as (MOP), (KOP) phine and morphine-6-glucuronide are eliminated by the kid-
and (DOP) and nociception/orphanin FQ (N/OFQ) peptide ney; therefore, renal dysfunction results in a prolonged drug
receptor (NOP). effect.
Opioids bind to the CNS and peripheral tissue receptors. Morphine may also cause hypotension due to vasodilatation
1-Receptors mediate analgesia, whereas 2-receptor bind- (secondary to the release of histamine).
ing produces respiratory depression, nausea, vomiting, consti-
pation, and euphoria. -Receptor activation causes sedation,
miosis, and spinal analgesia. In addition to analgesia, opioid Fentanyl
receptors may provide mild-to-moderate anxiolysis. Opioids
have no reliable amnestic effect on patients. Opioid admin- Fentanyl is highly lipid soluble with rapid onset of action
istration is associated with a dose-dependent, centrally medi- (1 minute) and rapid redistribution into peripheral tissues, re-
ated respiratory depression. The respiratory rate is reduced, sulting in a short half-life (0.5 to 1.0 hour) after a single dose.
whereas the tidal volume is initially preserved. The ventilatory The duration of action with small doses (50 to 100 g) is short
response to hypoxia is eradicated and the CO2 response curve as a result of redistribution from the brain to other tissues.
is shifted to the right. Opioids facilitate patients compliance to Larger or repeated doses, including the doses delivered via a
the ventilator due to their cough-suppressant effects. Despite continuous infusion, alter the context-sensitive half-time and
minimal cardiovascular effects in normovolemic patients, they result in drug accumulation and prolonged effects of the drug.
may generate hypotension via decreased sympathetic tone, and The hepatic metabolism of fentanyl creates inactive metabolites
thus may decrease heart rate and systemic vascular resistance that are renally excreted, making this drug a more attractive
in critically ill patients. Additionally, opioids increase venous choice in patients with renal insufficiency. Fentanyl causes mi-
capacitance, thereby decreasing venous return. Hypotension nor hemodynamic changes and does not affect inotropy.
clearly is more pronounced in hypovolemic patients.
Opioid-induced ileus is a common problem in critically ill
patients.
Hydromorphone
Hydromorphone is a semisynthetic opioid that is five- to ten-
Morphine fold more potent than morphine, but with a similar duration of
action. It has minimal hemodynamic effects, lacks a clinically
Morphine has poor lipid solubility and thus has a relatively significant active metabolite, and causes minor to no histamine
slow onset of action (5 to 10 minutes). The standard IV dose release [44]. Recently published data (Chang et al.) suggest
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Chapter 24: Management of Pain in the Critically Ill Patient 211

that patients who received IV hydromorphone have a greater propofol-based regimen are almost twice as likely to be
decrease in pain than those given an equianalgesic dose of IV extubated and discharged from the ICU within the first 3 days
morphine [45]. of treatment than patients on conventional regimens [53].
In addition, remifentanil does not exert significantly pro-
longed clinical effects when it is administered to ICU patients
Methadone with renal failure or chronic liver disease [49]. On the basis
of these studies, it can be concluded that remifentanil is ef-
Methadone is a synthetic opioid agent with properties sim- fective for providing both analgesia and sedation in critically
ilar to morphine. It can be given enterally and parenterally. ill patients, even those suffering from multiple organ failure.
Methadone is an attractive choice for opioid analgesia due to its However, further data are needed to better guide clinicians on
long half-life and low cost. It produces N-methyl-d-aspartate the use of this drug in ICU patients.
(NMDA) antagonism, which makes it ideal for neuropathic
pain. Although methadone is not the drug of choice for an
acutely ill patient whose hospital course is rapidly changing, it OPIOID SIDE EFFECTS
is a good alternative for the patient who has preexisting opioid
tolerance or prolonged ventilatory wean. It may help facilitate Opioid-related adverse effects occur commonly in the ICU [54].
the tapering of opioid infusions [46,47]. Metabolized in the Opioid-induced respiratory depression is generally dose re-
liver, 40% of the drug is eliminated from kidney and free from lated and is most deleterious for the spontaneously breathing
active metabolites. It does not accumulate in renal failure. ICU patients. Incidence of opioid-induced nausea and vomit-
ing is low in the ICU. High-dose fentanyl may cause muscle
rigidity. Opioid-induced hypotension occurs most commonly
Oxycodone in patients who are hemodynamically unstable, are volume de-
pleted, or have a high sympathetic tone. The use of morphine
Oxycodone is effective for postoperative pain management. It is associated with histamine release; therefore, hypotension,
has a higher bioavailability and a slightly longer half-life than urticaria, pruritus, flushing, and bronchospasm are possible.
oral morphine. When transferring patients from parenteral Fentanyl can safely be used in patients with a suspected al-
morphine to oral oxycodone, the dose should be based on a lergy to morphine. Excessive sedation from opioids is most
1:1.5 ratio (i.e., 1 mg IV morphine = 0.5 to 0.7 mg oral oxy- often seen with the use of continuous infusions, particularly
codone). Individual patient variability and incomplete cross- in patients with end-stage renal disease who are receiving fen-
tolerance requires careful titration [48]. tanyl or morphine. Methadone may cause excessive sedation
The use of controlled-release oxycodone (OxyContin) is in- if the dose is not titrated downward after the first 5 days of
dicated for the treatment of moderate-to-severe pain when con- therapy or if a human cytochrome P450 inhibitor is concomi-
tinuous analgesia is required for prolonged periods. The release tantly administered. QTc-interval prolongation and the risk
of oxycodone from the OxyContin capsule is biphasic; there of development of torsades de pointes can occur with high
is a rapid initial absorption phase within 37 minutes followed doses of methadone because of its effects on the hERG chan-
by a slow absorption phase over 6.2 hours. Peak pain relief for nel, particularly if the chlorbutanol-containing IV formulation
OxyContin capsules occurs at approximately 1 hour and lasts is used. Opioids may cause hallucinations, agitation, eupho-
for 12 hours, with peak plasma concentrations at 2 to 3 hours ria, sleep disturbances, and delirium [55]. Methadone may be
after administration. the least likely drug to cause delirium because of its antago-
nistic activity at the NMDA receptor [56]. The effects of opi-
oids on ICP in patients with traumatic brain injury remain un-
Remifentanil clear. Gastric retention and ileus are common in patients who
are critically ill and receiving opioids, with prokinetic therapy
Remifentanil (a derivative of fentanyl) is a powerful analgesic and/or postpyloric access required in patients prescribed en-
with ultrashort duration of action. It is metabolized by nonspe- teral nutrition. Prophylactic use of a stimulant laxative reduces
cific esterases to remifentanil acid, which has negligible activity the incidence of constipation. Methylnaltrexone, an opioid an-
in comparison. Its metabolism is independent from hepatore- tagonist specific to peripheral receptors, may have a role in
nal function. The context-sensitive half-time of remifentanil is treating opioid-induced constipation that fails to respond to
consistently short (3.2 minutes), even after an infusion of long laxative therapy [57]. The possibility of developing an addic-
duration up to 72 hours [49]. tion problem in adult patients receiving long-term opioids is
In terms of safety, efficacy, and speed of onset and offset, extremely low.
remifentanil has been reported to have a better profile when
compared to fentanyl [50]. When a morphine-based pain and
sedation regimen was compared to another based on remifen-
tanil, the mean duration of mechanical ventilation and ex- OPIOIDS ADMINISTRATION
tubation time were significantly shorter in the remifentanil METHODS
group [51]. Breen et al. [52] compared a remifentanil-based
analgesiasedation regimen with a midazolam-based one, to Opioid analgesics administered by either continuous infusion
which fentanyl or morphine could be added for analgesia, in a or titration to effect provide better pain control and less drug-
group of critically ill patients requiring prolonged mechanical related adverse effects. As needed protocols make it difficult
ventilation for up to 10 days. The remifentanil-based sedation to achieve adequate analgesic plasma concentrations with re-
regimen was associated with significantly reduced duration of sultant poor pain control.
mechanical ventilation by more than 2 days. When a continuous infusion is used, a sedation vacation
Rozendaal et al. reported that in patients with anticipated protocol allows more effective analgesic titration with a lower
short-term mechanical ventilation, a remifentanilpropofol total dose of opioid used. Daily awakening may also be as-
analgesiasedation regimen provides better control of seda- sociated with a shorter duration of ventilation and ICU stay.
tion and agitation and reduces weaning time compared to For patients in whom a long recovery and a prolonged ventila-
conventional regimens. In addition, patients on a remifentanil tory wean are anticipated, it is appropriate to use a long-acting
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212 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

medication (e.g., methadone) to achieve adequate background IV PCA allows the patient to self-administer a predeter-
pain control in combination with bolus doses of a short-acting mined dose of opioid within the limits of a lockout period.
opioid for management of breakthrough pain. This results in less variability in the blood levels of the drug,
thereby enabling titration of the drug to effect [58].
The epidural and intrathecal routes of administration pro-
Conventional Routes of Administration vide a more rapid analgesia due to the application of the drug
directly within the CNS.
(Oral, Intramuscular, and Subcutaneous) Patient-controlled epidural analgesia (PCEA) regimens al-
low better titration of the medication. In general, the analgesic
Because of first-pass metabolism in the liver, larger doses of efficacy of neuraxial opioids is greater than that achieved with
medications are required when oral preparations are used. parenteral opioid administration, resulting in superior pain
Immediate-release oral opioids (e.g., morphine, oxycodone, relief despite the smaller doses used in the subarachnoid or
and hydromorphone) are preferred because onset analgesia is epidural space (e.g., subarachnoid morphine 0.1 mg = epidu-
obtained in 45 to 60 minutes. Fixed-interval dosing (e.g., every ral morphine 1 mg = IV morphine 10 mg). Opioid solutions
4 hour) is preferable to a when required regimen to ensure with preservative-free formulations should be used for neurax-
adequate relief of moderate-to-severe pain. ial administration to avoid potential neurotoxicity.
The rectal route is rarely used in the ICU. Drugs absorbed Highly lipid-soluble opioids (e.g., fentanyl and buprenor-
from the lower half of the rectum bypass the portal vein and phine) have been formulated as a skin patch for transdermal
first-pass metabolism in the liver. Suppository formulations delivery, especially in the management of severe pain in chronic
containing morphine, oxycodone, hydromorphone, and oxy- and palliative care. Fentanyl patches are usually not a recom-
morphone are available. mended modality for acute analgesia because of their 12- to
Intramuscular injections of opioids are useful if there is a 24-hour delay to peak effect and similar lag time to complete
lack of personnel trained to administer IV injections or if ve- offset once the patch is removed. However, it is appropriate
nous access is difficult. The intramuscular injection of mor- to continue its use in the ICU if the patient has a known
phine takes 30 to 60 minutes to be effective. Absorption of history of using this formulation of the medication prior to
intramuscular opioids is variable and depends on the injection admission.
site, especially in the critically ill patients. Technological advances have led to the development of a
Subcutaneous injection via an indwelling cannula in the sub- transdermal delivery system that uses ionophoresis for the
cutaneous tissue of the upper outer aspect of the arm or thigh management of acute postoperative and post-trauma pain. This
is a useful alternative route of administration. The rate of ab- is a compact, self-contained, and self-adhesive system, which
sorption of morphine after subcutaneous injection is similar to is applied to the patients upper arm or chest. The system is
that of an intramuscular injection; therefore, the guidelines for preprogrammed and uses an imperceptible electric field to de-
titration are the same (Fig. 24.1). liver 40 g of fentanyl over 10 minutes and is unresponsive to
additional dose requests during this time; patients can initiate
up to 6 doses per hour for a 24-hour period or a maximum of
Advanced Methods of Administration 80 doses per system, whichever occurs first. Numerous trials
have already demonstrated fentanyl iontophoretic transdermal
The IV route is the preferred route of administration. There is system (ITS) to be better than placebo and therapeutically com-
less variability in blood levels when the IV route is used, making parable with a standard morphine IV PCA. The pharmacoki-
it easier to titrate the drug to effective analgesia concentration. netics is similar to those of IV fentanyl [59,60]. Its release waits
IV infusions are a commonly used method. An opioid infu- completion of further clinical trials.
sion at a fixed rate takes five half-lives of the drug to reach 98%
of a steady-state concentration. Therefore, a front-loading dose Other Drugs
is needed to achieve adequate pain relief more rapidly before
starting the infusion. If breakthrough pain occurs, more IV bo- Adjuvants are compounds which by themselves have undesir-
lus doses may be needed to reestablish pain relief before the able side effects or low potency, but in combination with opi-
infusion rate is increased. oids, allow a reduction of opioid dosing for pain control.

Five-Point Global Scale None Ketamine


A little = 1
Some = 2 Ketamine is a dissociative anesthetic also used for sedation.
A lot = 3 It possesses strong analgesic properties. It acts both centrally
The worst = 4 and peripherally by inhibition of glutamate activation via non-
competitive antagonism at the phencyclidine receptor of the
NMDA channel. Nitric oxide (NO) synthase inhibition also
Verbal Quantitative Scale 0.5.10 contributes to its effects.
None Worst imaginable
Water- and lipid-soluble characteristics of ketamine hy-
drochloride enable the IV, intramuscular, subcutaneous, epidu-
ral, oral, rectal, and transnasal routes of administration. It
Visual Pain Analog Scale No Worst has a rapid onset and short duration of action [61]. Follow-
.. ing metabolism in the liver, norketamine is produced, which
Pain Pain is significantly less potent (20% to 30%) when compared to
ketamine.
Place a mark on the line In subanesthetic or low doses (0.1 to 0.5 mg per kg
FIGURE 24.1. Several scales that can be useful for the evaluation of IV), ketamine demonstrates significant analgesic efficacy with-
patient self-reports of pain before and after treatment. [From Stevens out significant adverse pharmacologic effects. There is evi-
DS, Edwards WT: Management of pain in the critically ill. J Intensive dence that low-dose ketamine may play an important role in
Care Med 5:258, 1990, with permission.] postoperative pain management when used as an adjunct to
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Chapter 24: Management of Pain in the Critically Ill Patient 213

opioids, local anesthetics, and other analgesic agents [6264]. shown a positive effect of the gabapentinoids on postoperative
Administration of regular benzodiazepines should be consid- pain in humans. Single doses of gabapentin up to 1,200 mg
ered to minimize the psychomimetic side effects associated with have been shown to reduce pain scores and/or morphine con-
its use. sumption after abdominal and vaginal hysterectomy, lower
Subhypnotic doses of ketamine administered as infusions limb arthroplasty, and laparoscopic cholecystectomy. Differ-
have been used for critically ill ICU patients who are very ent meta-analyses have confirmed these effects, which persist
difficult to sedate with opioid and benzodiazepine infusions. for up to 24 hours after surgery [72]. Common side effects
Because of its potential adverse effects, ketamine is not rec- of these medications include dizziness and drowsiness, which
ommended for routine sedation and analgesia of the critically should not limit its use in ICU. Gabapentin has minimal drug
ill patient, but it can be useful for more difficult situations interactions.
and/or when short surgical procedures with intense pain, such Pregabalin has the same mechanism of action as that of
as placement of chest tubes, dressing changes, and/or wound gabapentin. It has higher efficacy due to its linear pharmacoki-
debridement in burn patients, are necessary. netics. In addition, pregabalin appears to have a faster onset of
action, which is due in part to its smaller volume of distribu-
tion.
2 -Adrenergic Agonists Perioperative gabapentinoids (gabapentin/pregabalin) re-
duce postoperative pain, opioid requirements, and the inci-
2 -Adrenergic activation represents an intrinsic mechanism of dence of opioid-related adverse effects, but increase the risk
pain control at the level of the CNS. 2 -Adrenergic receptors of sedation.
exist in large numbers in the substantia gelatinosa of the spinal
cord dorsal horn in humans. Agonists produce their pain con-
trol effect on those receptors. REGIONAL ANALGESIA
TECHNIQUES
Clonidine Recent studies suggest that advances in perioperative anesthe-
sia and analgesia improve pain relief, patient satisfaction, and
Clonidine produces analgesia after systemic, epidural, or in- outcome in surgical and trauma patients. Neuraxial anesthesia
trathecal administration. It has a short duration of action af- and peripheral nerve blockade have the potential to reduce or
ter a single dose and may produce sedation, bradycardia, and eliminate the physiologic stress response to surgery and trauma,
hypotension. Clonidine improves opioid analgesia and poten- decreasing the possibility of surgical complications and im-
tiates the effect of local anesthetic [65,66]. proving outcomes.
When used alone or in combination with other treatment
modalities, regional analgesia techniques are an invaluable tool
Dexmedetomidine to address pain-related problems in critically ill patients, but
the indications for their use must be established correctly. ICU
Dexmedetomidine is a centrally acting 2 -agonist with seda- patients are at risk for numerous complications and the use of
tive and analgesic properties. It has a much greater affinity for an inappropriate regional analgesia technique can cause a dete-
2 -receptors than clonidine. The sedative properties are facili- rioration of the patients clinical status, affecting a potentially
tated through the locus coeruleus in the CNS. Analgesic effects favorable outcome.
occur via activation of the 2 -receptors and through potenti- The purpose of this section is to discuss risk and benefits of
ation of the action of opioids [67]. The drug causes no sig- neuraxial and peripheral nerve blockade for the management
nificant effect on the respiratory drive even when used with of pain in the critically ill patient.
opioids. Dexmedetomidine has a biphasic effect on the cardio-
vascular system. The initial bolus injection is associated with
vasoconstrictive effects, causing bradycardia and hypertension. General Considerations
Continuous infusion is associated with hypotension secondary
to vasodilation caused by central sympatholysis. Studies con- The use of ultrasound (US) technology in regional anesthesia
ducted in postoperative ICU patients demonstrated successful allows a easier and more reliable identification of neural struc-
short-term sedation and analgesic sparing [68]. There are a tures, the safe administration of lower doses of local anesthetic,
few studies examining long-term administration to critically and the insertion of nerve catheters even in the heavily se-
ill, mechanically ventilated patients with encouraging results dated ICU patients. Ultrasound-guided (USG) techniques have
[69]. Suggested dosing recommendation would be a loading reduced misplacement and failure rates in clinical practice. Ef-
dose of 1 g per kg over 10 minutes followed by an infusion fective identification of the needle allows for the reduction of
at a rate of 0.2 to 0.7 g per kg per hour. the amount of administered drug volumes, which may be of
importance in the critically ill, children, and patients who need
more than one block, especially for those who have undergone
Anticonvulsants multisite surgery or sustained multitrauma [73].
Regional analgesia techniques also effectively block sympa-
Gabapentin and pregabalin are licensed for the management thetic outflow. Many studies show that surgically related stress
of neuropathic pain. is reduced when regional anesthesia and analgesia techniques
Despite its structural similarity to GABA, gabapentin does are used, neuraxial techniques in particular. The use of neu-
not bind to GABA receptors. It has a high affinity for 2 /- raxial analgesia has also been reported to decrease the rate
subunits of voltage-dependent calcium channels, resulting in of postoperative myocardial infarctions, shorten postoperative
postsynaptic inhibition of the calcium influx and thereby reduc- and post-traumatic ileus, improve the outcome, and shorten
ing the presynaptic excitatory neurotransmitter release [70]. It the length of ICU stay [74].
markedly decreases postoperative opioid consumption when The use of such techniques may also reduce the incidence of
given at the time of anesthetic induction [71]. Several random- chronic pain in patients undergoing surgical procedures, such
ized controlled trials (RCTs) using different pain models have as limb amputations and thoracotomies, two procedures in
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214 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

particular associated with the development of chronic persis- complications after thoracic or lumbar PVB was reported to
tent postsurgical pain [75]. be as follows: hypotension 5%, vascular puncture 3.8%, pleu-
ral puncture 0.9%, and pneumothorax 0.3% [79,80].

Nerve Blocks for Thoracic Interpleural Analgesia


and Abdominal Wall Interpleural blockade is a technique by which an amount of lo-
cal anesthetic is injected into the thoracic cage between the pari-
Intercostal Nerve Blocks etal and visceral pleura to produce ipsilateral somatic block of
Single and continuous intercostal nerve blocks are used to pro- multiple thoracic dermatomes. Local anesthetic solutions can
vide analgesia in patients with thoracic injuries and rib frac- be administered as single or intermittent boluses, or as continu-
tures and for the treatment of postoperative pain. Excellent ous infusions via an indwelling interpleural catheter. It has been
pain relief and improvement in pulmonary mechanics have shown to provide safe, high-quality analgesia after cholecys-
been reported [76]. tectomy, thoracotomy, renal surgery, breast surgery, and some
Intercostal nerve blocks are associated with risk of pneu- invasive radiologic procedures of the renal and hepatobiliary
mothorax and systemic local anesthetic toxicity. The patients system. It has also been used successfully in the treatment of
coagulation status must be checked to prevent the risk of bleed- pain from multiple rib fractures, herpes zoster, CRPS, thoracic
ing and hematoma formation subsequent to the laceration of and abdominal cancer, and pancreatitis [80].
an intercostal vessel. There are several methods proposed for the detection of the
Continuous intercostal nerve blockade after thoracotomy entry of the needle into the pleural space. All of them involve the
using an extrapleural catheter consistently results in better detection of the negative pressure of the intrapleural space
pain relief and preservation of pulmonary function than the [81]. If a posterior approach is not possible, an anterior ap-
use of systemic opioids and appears to be at least as effective proach could be used. The catheter may also be positioned in
as the relief provided by the epidural approach. The ease of the interpleural space under direct vision during surgery.
the extrapleural approach and the low incidence of compli- The risk of pneumothorax is 2%. The risk of systemic local
cations suggest that this technique should be used more fre- anesthetic toxicity is 1.3%. Pleural inflammation increases the
quently. Other methods of intercostal nerve blockade appear risk of toxicity. Interpleural blocks have no clinically significant
to be less effective. The use of a multifaceted approach to post- adverse effect on respiratory muscle function; on the contrary,
thoracotomy analgesia that includes intercostal nerve blockade they are more likely to be beneficial in the presence of painful
has been shown to be beneficial in the immediate postoperative conditions compromising pulmonary function.
period, as well as reduce the incidence of chronic pain. It has been suggested that local anesthetic solution diffuses
Major pulmonary resections, which have been managed outward with the interpleural technique blocking multiple in-
with a minithoracotomy and intrapleural intercostal nerve tercostal nerves, the sympathetic chain of the head, neck and
blocks, have been shown to be associated with reduced post- upper extremity, the brachial plexus, splanchnic nerves, the
operative pain and improved outcome. However, a recently phrenic nerve, the celiac plexus, and ganglia. As the injected
published study in thoracotomy patients did not find a mea- local anesthetic diffuses out through both layers of the pleura,
surable difference in pain relief between intercostal catheters direct local effects on the diaphragm, lung, pericardium, and
and epidural analgesia [77]. peritoneum may also contribute to some of its analgesic activity
Although not frequently used, intercostal nerve blocks can [81].
be extremely useful in the ICU patient, especially when used
as a single injection for painful procedures (e.g., placement of Transversus Abdominis Plexus Block
chest tubes), or as an infusion when the patients hemodynamic
conditions do not allow the use of thoracic epidural analgesia Incisional pain represents a considerable portion of postop-
(TEA). erative pain following abdominal operations. The abdominal
wall consists of three muscle layers: external oblique, internal
oblique, transversus abdominis, and their corresponding fas-
Paravertebral Block cial sheaths. The skin, muscles, and parietal peritoneum of the
Paravertebral nerve blocks (PVBs) provide analgesia for tho- anterior abdominal wall are innervated by the lower six tho-
racic and upper abdominal pain. Paravertebral nerve block- racic nerves and the first lumbar nerve. The anterior primary
ade can be performed with a single injection or a continuous rami of these nerves exit their respective intervertebral foram-
catheter technique [78]. Injection of contrast material into a ina and extend over the vertebral transverse process. They then
paravertebral catheter shows flow of the dye laterally into the pierce the musculature of the lateral abdominal wall to travel
intercostal space, as well as up and down the ipsilateral par- through a neurofascial plane between the internal oblique and
avertebral space, leading to the spreading of local anesthetics transversus abdominis muscles.
over several dermatomal levels. Deposition of local anesthetic dorsal to the midaxillary line
The advantages of PVBs are similar to those of the inter- blocks both the lateral cutaneous branch and the lateral cuta-
costal nerve block technique. Analgesia can be obtained with- neous afferents, thus facilitating blockade of the entire anterior
out widespread cardiovascular effects because only unilateral abdominal wall. The transversus abdominis plane (TAP) thus
sympathetic blockade is produced. provides a space into which local anesthetic can be deposited
Because the site of injection is medial to the scapula, this to achieve myocutaneous sensory blockade.
block is easier to perform at high thoracic levels than the inter- This regional technique has been shown to provide good
costal nerve blocks. In contrast to routine intercostal blocks, postoperative analgesia for a variety of procedures involv-
the posterior primary ramus of the intercostal nerve is also cov- ing the abdominal wall [82]. The use of a fine-gauge, blunt-
ered with the paravertebral approach, providing analgesia of tipped, short-bevel needle, and USG has been proposed to re-
the posterior spinal muscles and the costovertebral ligaments. duce the incidence of possible complications (intraperitoneal
Failure rate after PVB in adults varies from 6.1% to 10.7% injection with bowel injury/hematoma, liver laceration, tran-
and compares favorably with other regional procedures. In sient femoral nerve palsy, accidental intravascular injection,
a prospective study of 319 adult patients, the incidence of infection, and catheter breakage). In addition, with USG
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Chapter 24: Management of Pain in the Critically Ill Patient 215

techniques, upper and lower portions of the abdominal wall position and enables more secure placement of a peripheral
can be preferentially blocked [83]. nerve catheter with high success rate.

Peripheral Nerve Blocks Epidural Analgesia


for the Upper Extremities Epidural analgesia is the most frequently used regional anesthe-
sia technique in the ICU [92] and has been reported to provide
Severe trauma to the shoulders and arms is frequently present
better pain relief than parenteral opioid administration [93].
in acutely injured ICU patients. These injuries may be associ-
However, literature data report conflicting evidence regarding
ated with blunt chest trauma requiring mechanical ventilation;
reduction of mortality with the use of epidural analgesia. The
they usually augment pain overall, especially during position-
largest meta-analysis (CORTRA) [74] to date and analysis of
ing [84]. If the orthopedic injury is part of a complex trauma
the Medicare claims database [94] indicate a reduction in pe-
with closed-head injury causing alterations of the mental status
rioperative mortality with perioperative neuraxial anesthesia.
so that opioid-based analgesia regimens may mask the under-
Procedure-specific meta-analyses and specific RCTs, however,
lined neurologic condition, adequate analgesia can be provided
have not demonstrated benefit from epidural anesthesia and
with blocks of the brachial plexus.
analgesia regarding reduction in mortality. It is important to
Continuous brachial plexus blocks consistently provide su-
note that these specific meta-analyses and individual RCTs lack
perior analgesia with minimal side effects, promoting earlier
sufficient sample size due to the relatively low incidence of mor-
hospital discharge and possibly improving rehabilitation after
tality (0.2% to 5%) overall [95].
major surgery [85].
A meta-analysis of more than 5,000 surgical patients [96]
Peripheral nerve injury is a rare complication of regional
has shown that postoperative epidural analgesia reduces the
anesthesia for the upper extremities. A large study from France
time to extubation, length of ICU stay, incidence of renal fail-
reported 0.04% overall risk of a serious adverse event after pe-
ure, morphine consumption during the first 24 hours, and max-
ripheral nerve block [86]. Several retrospective studies reported
imal glucose and cortisol blood concentrations, and improves
the incidence to be between 0.5% and 1.0%, whereas prospec-
forced vital capacity. Many of these benefits may be relevant
tive studies published higher incidence rates between 10% and
to ICU patients; they have been demonstrated to be actually
15% [87].
beneficial in cardiac surgery [97] and thoracic trauma patients
Current evidence suggests that peripheral nerve blocks
[98], as well as patients with severe acute pancreatitis [99].
should not be routinely performed in most adults during gen-
Whether sepsis, with or without positive blood cultures,
eral anesthesia (GA) or heavy sedation especially when using
should be an absolute contraindication for the use of epidural
the interscalene approach. However, the risk-to-benefit ratio of
analgesia is still a matter of debate [100]. In patients with is-
performing a peripheral nerve block under these conditions ver-
chemic heart disease, high thoracic epidural analgesia (HTEA)
sus using high doses of opioids to maintain adequate analgesia
has been shown to improve systolic and diastolic myocardial
should be carefully considered in select ICU patients [88].
function [101]. Furthermore, Ferguson et al. have concluded, in
Furthermore, the advent of USG techniques, in combination
a recently published prospective randomized trial, that PCEA
with injection pressure monitoring and electric nerve stimula-
offers superior postoperative pain control after laparotomy for
tion, may help to significantly minimize possible serious com-
gynecologic surgery compared to traditional IV PCA [102].
plications in heavily sedated patients with increased success
TEA exerts a remarkable influence on the cardiovascu-
rate and potential benefits overall.
lar system. It reduces the risk of perioperative dysrhythmias
except postoperative atrial fibrillation. In cardiac surgical pa-
tients, with improved left ventricular function, the left ventricu-
Peripheral Nerve Blocks lar global and regional wall motions are better preserved. TEA
for the Lower Extremities has been associated with a reduction of cardiac oxygen con-
sumption without jeopardizing coronary perfusion pressure
Lower extremity injuries are also commonly present in criti- with an increase of the diameter of stenotic coronary segments.
cally ill ICU patients. As a result, TEA reduces the overall incidence of myocardial
Reid et al. recently conducted a study to compare the ac- infarction. It produces functional hypovolemia by inhibiting
curacy, success rates, and complications of USG femoral nerve the vasoconstrictor sympathetic outflow; moreover, it interferes
blocks (FNBs) with the fascial pop (FP) technique in an emer- with the integrity of reninangiotensin system, but increments
gency department. The result of this study favors the use of vasopressin plasma concentration. Despite causing hypoten-
USG FNB. A similar study, conducted by Marhofer et al. has sion, TEA has a beneficial outcome during hemorrhagic shock
demonstrated a clear benefit in the use of US over a peripheral [103].
nerve stimulator when performing a three-in-one nerve block. Issues of consent, coagulopathy, and infection can be ad-
FNB is the preferred analgesic technique following injuries dressed easily in elective conditions; they become a major prob-
of the knee. Compared to epidural analgesia, it has a favor- lem in patients with multiple trauma or extremely painful con-
able morbidity profile, it allows early mobilization, and there ditions (e.g., acute pancreatitis).
is no need for urinary catheterization. In addition, with USG, A study published in Sweden reports the risk of hematoma
the technique is simple and easy to perform compared to the to be 1.3 to 2.7 per 100,000 [104]. The current recommenda-
epidural blocks [89]. FNB and catheters are helpful in the man- tions of the American Society of Regional Anesthesia should
agement of acute pain following femoral fractures as well as be followed [105].
after surgical stabilization [90]. Placing epidural catheters safely and confirming the pres-
Easy visualization of the sciatic nerve proximal to the ence of an adequate sensory block can be difficult in critically
popliteal fossa, before it divides into common peroneal nerve ill, sedated, and anesthetized patients. Awake and cooperative
medially and tibial nerve laterally with USG, makes the lateral patients usually facilitate the placement of an epidural catheter,
approach to the sciatic nerve an ideal approach for manage- minimizing the possibility of undesirable complications. Cur-
ment of pain secondary to distal tibia, ankle, and foot fractures rent recommendations suggest that the possibility to miss sys-
[91]. This block can be conveniently performed in the supine temic local anesthetic toxicity under GA or heavy sedation is
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216 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

not a valid reason not to perform a neuraxial block in this group


of patients. However, neuraxial regional anesthesia should be Endocrine Effects
performed rarely in patients whose sensorium is compromised Catabolic and anabolic changes
by GA or heavy sedation [88]. The overall risk of neuraxial Decrease in insulin production
anesthesia should be weighed against its expected benefit. Reduction in testosterone level
Positioning the patient for the procedure may also repre- Fluid retention
sent a challenge depending on the underlying injury and the
number and position of tubes, catheters, or external fixation
devices present. Strict asepsis should always be maintained for
neuroaxial procedures.
Metabolic Effects
Bolus injections of long-acting local anesthetics, such as Raised blood sugar level
bupivacaine and ropivacaine, or the discontinuation of contin-
uous infusions every morning can help neurologic and sensory
assessment. Gastrointestinal effects
The most common side effects of thoracic epidural blocks
are bradycardia and hypotension related to sympathetic block; Delayed gastric emptying
this can be more pronounced with intermittent bolus dosing in Nausea
patients with hypovolemia or shock. Continuous low-rate local Reduced GI motility and ileus
anesthetic and/or opioid (morphine) infusions can be safely
used in this particular clinical setting.
Currently, sepsis and bacteremia are considered contraindi- Coagulation
cations to neuraxial blockade. Fever and increased white blood
cell count alone in the absence of positive blood cultures do Immobility
not provide a reliable diagnosis of bacteremia. High levels Increased blood viscosity
of the serum markers C-reactive protein, procalcitonin, and Hypercoagulability and deep vein thrombosis (DVT)
interleukin-6/8 have been shown to indicate bacterial sepsis
with a high degree of sensitivity and specificity and can guide A meta-analysis published in the year 2000 has concluded
the decision as to whether or not to place an epidural catheter that epidural analgesia prevents postoperative major compli-
[106]. cations and may decrease postoperative mortality [74]. Other
Because high-risk patients seem to profit most from epidu- studies have reported that epidural anesthesia may selectively
ral analgesia and the current literature does not address the prevent the occurrence of respiratory and cardiovascular com-
specific problem of the critically ill patient with multiple co- plications [107109].
morbidities and organ failure, logic suggests that in carefully Recent prospective trials, including a significant number of
selected and closely monitored patients epidural analgesia may patients, have failed to confirm the beneficial effect of epidu-
have significant benefits. Further research is needed before clear ral anesthesia on postoperative morbidity and mortality after
recommendations can be made. major abdominal or orthopedic surgery. Such a discrepancy
is thought to be the result of improved postoperative medi-
cal care. As an example, previously reported 50% reduction
INFLUENCE OF PAIN in DVT with epidural analgesia is no longer a valid criterion
due to the recent introduction of low-molecular-weight hep-
MANAGEMENT ON arin (LMWH) for management of DVT prophylaxis, which
COMPLICATIONS, OUTCOME, decreases the risk by more than 80%. Similarly, the use of pro-
phylactic antibiotics and aggressive physiotherapy significantly
LENGTH OF HOSPITAL STAY, AND reduces the postoperative pulmonary complications, and the
CHRONIC PAIN preventive effect of epidural analgesia on chest infections has
become less important.
Pain leads to development of increased catabolism, immuno- Consequently, there is no significant evidence to consider
suppression, and prolonged sympathetic response as a result of epidural analgesia beneficial for the prevention of morbidity,
the combination of tissue injury and pain that leads to increased but as part of a multimodal pain management process, it may
morbidity and mortality. These effects can be subclassified as facilitate recovery from surgery. The superior quality of pain
follows. relief provided by epidural analgesia combined with parenteral
analgesia does indeed have a positive impact on mobilization,
bowel function, and early food intake that results in a signifi-
Cardiovascular Effects cant improvement in postoperative quality of life [110]. In or-
thopedic surgery, regional analgesia may provide a functional
Increased heart rate benefit, allowing better patient involvement with physical ther-
Increased blood pressure apy and shorter recovery.
Increased stroke volume Hebl et al. [111] have published their findings on the im-
Increased myocardial O2 demands and reduced supply lead- provements in perioperative outcomes following peripheral
ing to myocardial ischemia nerve block after major orthopedic surgery. These include sig-
nificantly shorter hospital stay, earlier ambulation, improved
joint range of motion, lower perioperative pain scores, and a re-
Respiratory Effects duction in postoperative nausea and vomiting when compared
with patients treated with traditional postoperative IV opioids
Stimulation of respiration causing initial hypocapnia and (PCA). These patients also had significantly lower opioid re-
respiratory alkalosis quirements when compared with controls, as well as significant
Diaphragmatic splinting and hypoventilation, atelectasis, reduction in urinary retention and postoperative ileus [111].
hypoxia, and hypercapnia Although the risk factors are difficult to identify, patients
Development of chest infection who experience severe pain and, above all, persistence of
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Chapter 24: Management of Pain in the Critically Ill Patient 217

postoperative pain several days after the expected duration are agement specialists and anesthesiologists is often necessary for
prone to develop chronic pain. the management of these complex situations.
Postoperative chronic pain is defined as persisting pain, Choosing the treatment plan that best fits the patients clin-
without relapse or pain-free interval, 2 months after the surgi- ical conditions is mandatory. A potentially favorable outcome
cal insult. Chronic pain syndromes have been described com- can be altered if inappropriate pain modalities are chosen and
monly after breast surgery, inguinal hernia repair, cholecys- used.
tectomy, thoracic surgery, cardiac surgery, and limb or organ A rational multimodal approach including the use of non-
amputation. Its incidence has been recorded to be up to 60% pharmacologic, pharmacologic, and regional analgesia tech-
[112]. With such a high incidence, it is very important to pro- niques is desirable and often needed. The continued use of these
vide good postoperative and post-trauma pain control to pre- techniques extended into the postoperative period may shorten
vent the occurrence of chronic pain syndromes. recovery time and speed discharge.
Always assess and monitor the effects of a treatment modal-
ity on the patients pain and clinical conditions as well. Be pre-
pared to make changes in therapy as needed.
CONCLUSIONS Regional analgesia techniques (epidural and peripheral
nerve blockade), although proved to be safe and effective, are
Pain control in critically ill patients is of paramount impor- underused in the management of pain in critically ill patients.
tance. Achieving adequate levels of analgesia in trauma and They allow a decrease in the overall use of opioid analgesics
surgery patients decreases the stress response and improves and sedatives and reduce the possibility of developing poten-
morbidity and mortality. tially dangerous side effects. A correct indication, as well as an
Individual units and acute pain teams should employ pain appropriate timing for their use, is required in order to increase
assessment techniques for patients with cognition impairment. their beneficial effects.
Lack of education, fear of possible side effects, and inappro- The availability of new technologies (e.g., ultrasonography)
priate use of medications contribute to the ineffective treatment improves the quality and safety of upper and lower extremity
of pain in critically ill ICU patients. The expertise of pain man- peripheral nerve blocks even in heavily sedated ICU patients.

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P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 25: Therapeutic Paralysis 219

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CHAPTER 25 THERAPEUTIC PARALYSIS


KHALDOUN FARIS

The most common indications for the use of neuromuscu- membrane and the postsynaptic end plate contain specialized
lar blocking agents (NMBAs) in the intensive care unit (ICU) nicotinic ACh receptors (nAChRs). The chemical signal is con-
include emergency or elective intubations, optimization of verted into an electric signal by binding of two ACh molecules
patientventilator synchrony, management of increased in- to the receptor (- and -subunits), causing a transient influx
tracranial pressure, reduction of oxygen consumption, and of sodium and calcium, and efflux of potassium from muscle
treatment of muscle spasms associated with tetanus. Accord- cells. This depolarization propagates an action potential that
ing to the American College of Critical Care Medicine and the results in a muscle contraction. Unbound ACh is quickly hy-
Society of Critical Care Medicine clinical practice guidelines drolyzed in the synapse by the enzyme acetylcholinesterase to
for sustained neuromuscular blockade in the adult critically ill acetic acid and choline, thus effectively controlling the dura-
patient, these medications should be used only when all other tion of receptor activation. A repolarization of the motor end
means of optimizing a patients condition have been used. This plate and muscle fiber then occurs.
recommendation is based on the concern that the administra-
tion of NMBAs may worsen patient outcome when adminis-
tered during a course of critical illness, particularly if the patient THE NICOTINIC
is receiving systemic steroids at the same time [1]. In a recent
international multicenter trial, 13% of patients on mechanical ACETYLCHOLINE RECEPTOR
ventilation received NMBAs for at least 1 day, which was asso-
The nAChR is built of five subunit proteins, forming an ion
ciated with a longer duration of mechanical ventilation, longer
channel. This ionic channel mediates neurotransmission at the
weaning time and stay in the ICU, and higher mortality [2].
NMJ, autonomic ganglia, spinal cord, and brain. During early
In addition to the pharmacology of the most commonly ad-
development, differentiation and maturation of the NMJ and
ministered agents, we briefly review the biology of the neu-
transformation of the nAChR take place: fetal nAChRs gradu-
romuscular junction (NMJ), its alterations during the course
ally disappear with a rise of new, functionally distinct, mature
of critical illness, and the resulting implications for the use
nAChRs.
of depolarizing and nondepolarizing NMBAs. Recommenda-
These mature nAChRs (also termed adult, innervated, -
tions for administration of NMBAs to ICU patients on based
containing) have a subunit composition of two , , , and
on available evidence are provided.
in the synaptic muscle membrane. The only structural dif-
ference from the fetal nAChR is in substitution of the
for the -subunit, although functional, pharmacologic, and
PHARMACOLOGY OF NMBAS metabolic characteristics are quite distinct. Mature nAChRs
have a shorter burst duration and a higher conductance to Na+ ,
The NMJ consists of the motor nerve terminus, acetylcholine K+ , and Ca2+ and are metabolically stable with a half-life av-
(ACh), and muscle end plate. In response to neuronal action eraging about 2 weeks. The two -, -, -, and / -subunits
potentials, ACh is released from presynaptic axonal storage interact to form a channel and an extracellular binding site for
vesicles into the synapse of the NMJ. Both the presynaptic ACh and other mediators as well. As mentioned previously,
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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220 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

simultaneous binding of two ACh molecules to - and - sis of chemical structure: benzylisoquinoliniums and aminos-
subunits of an nAChR initiates opening of the channel and a teroids. Within each of these classes, the therapeutic agents
flow of cations down their electrochemical gradient. In the ab- may further be categorized as short-acting, intermediate-acting,
sence of ACh or other mediators, the stable closed state (a major or long-acting agents. The benzylisoquinolinium agents com-
function of / -subunits) normally precludes channel opening monly used in the critical care setting include atracurium,
[3]. cisatracurium, and doxacurium, whereas the aminosteroid
Adult skeletal muscle retains the ability to synthesize not agents include vecuronium, rocuronium, pancuronium, and
only adult, but also fetal (often called immature or extrajunc- pipecuronium.
tional)-type nAChRs. The synthesis of fetal nAChRs may be The nondepolarizing NMBAs are administered by the intra-
triggered in response to altered neuronal input, such as loss of venous route and have volumes of distribution (Vd s) ranging
nerve function or prolonged immobility, or in the presence of from 0.2 to 0.3 L per kg in adults.
certain disease states. The major difference between fetal- and A clinical relationship exists between the time to onset of
adult-type nAChRs is that fetal receptors migrate across the paralysis and neuromuscular blocker dosing, drug distribution,
entire membrane surface and adult ones are mostly confined to and ACh-receptor sensitivity. An important factor to consider
the muscle end plate. In addition, these fetal nAChRs have a is Vd , which may change as a result of disease processes. Cir-
much shorter half-life, are more ionically active with prolonged rhotic liver disease and chronic renal failure often result in an
open channel time that exaggerates the K+ efflux, and are much increased Vd and decreased plasma concentration for a given
more sensitive to depolarizing agents such as succinylcholine dose of water-soluble drugs. However, drugs dependent on re-
and resistant to nondepolarizing neuromuscular blockers. nal or hepatic excretion may have a prolonged clinical effect.
The functional difference between depolarizing and nonde- Therefore, a larger initial dose but smaller maintenance dose
polarizing neuromuscular blockers lies in their interaction with may be appropriate.
AChRs. Depolarizing neuromuscular blockers are structurally Alterations in Vd affect both peak neuromuscular blocker
similar to ACh and bind to and activate AChRs. Nondepolar- serum concentrations and time to paralysis. The pharma-
izing neuromuscular blockers are competitive antagonists. cokinetic and pharmacodynamic principles of commonly used
NMBAs are summarized in Table 25.1.

DEPOLARIZING Atracurium
NEUROMUSCULAR BLOCKERS
Atracurium is an intermediate-acting nondepolarizing agent.
Succinylcholine is the only depolarizing neuromuscular blocker Neuromuscular paralysis typically occurs between 3 and 5 min-
in clinical use. Its use is limited to facilitating rapid-sequence utes and lasts for 25 to 35 minutes after an initial bolus dose.
intubation in the emergency setting. Succinylcholine mimics the Atracurium undergoes ester hydrolysis as well as Hofmann
effects of ACh by binding to the ACh receptor and inducing a degradation, a nonenzymatic breakdown process that occurs
persistent depolarization of the muscle fiber. Muscle contrac- at physiologic pH and body temperature, independent of re-
tion remains inhibited until succinylcholine diffuses away from nal or hepatic function. Renal and hepatic dysfunction should
the motor end plate and is metabolized by serum (pseudo-) not affect the duration of neuromuscular paralysis. The neu-
cholinesterase [4]. The clinical effect of succinylcholine is a roexcitatory metabolite laudanosine is renally excreted. Lau-
brief excitatory period, with muscular fasciculations followed danosine is epileptogenic in animals and may induce central
by neuromuscular blockade and flaccid paralysis. The intra- nervous system (CNS) excitation in patients with renal failure
venous dose of succinylcholine is 1 to 1.5 mg per kg and of- who are receiving prolonged atracurium infusions. Atracurium
fers the most rapid onset of action (60 to 90 seconds) of the may induce histamine release after rapid administration.
NMBAs. Recovery to 90% muscle strength after an intra-
venous dose of 1 mg per kg takes from 9 to 13 minutes. Suc-
cinylcholine is also suitable for intramuscular administration, Cisatracurium
most frequently for the treatment of laryngospasm in pediatric
patients without intravenous access; however, there are several Cisatracurium and atracurium are similar intermediate-acting
limitations. First, the required dose is higher (4 mg per kg) nondepolarizing agents. A bolus dose of 0.2 mg per kg of
and time to maximum twitch depression is significantly longer cisatracurium usually results in neuromuscular paralysis within
(approximately 4 minutes). Second, the duration of action of 1.5 to 2.5 minutes and lasts 45 to 60 minutes. When compared
succinylcholine after intramuscular injection is prolonged. with atracurium, cisatracurium is three times as potent and
Potential adverse drug events associated with succinyl- has a more desirable adverse drug event profile, including lack
choline include hypertension, arrhythmias, increased in- of histamine release, minimal cardiovascular effects, and less
tracranial and intraocular pressure, hyperkalemia, malignant interaction with autonomic ganglia. It also undergoes ester hy-
hyperthermia, myalgias, and prolonged paralysis. Neuromus- drolysis as well as Hofmann degradation. However, plasma
cular blockade can persist for hours in patients with genetic laudanosine concentrations after cisatracurium administration
variants of pseudocholinesterase isoenzymes [5]. Contraindi- are five to ten times lower than those detected after atracurium
cations to succinylcholine use include major thermal burns, administration [7,8].
significant crush injuries, spinal cord transection, malignant
hyperthermia, and upper or lower motor neuron lesions. Cau-
tion is also advised in patients with open-globe injuries, renal Rocuronium
failure, serious infections, and near-drowning victims [6].
Rocuronium is the fastest onset, shortest acting aminosteroidal
NMBA. A bolus dose of 0.6 mg per kg usually results in neu-
NONDEPOLARIZING NMBAS romuscular paralysis within 60 to 90 seconds. It may be con-
sidered an alternative to succinylcholine for rapid-sequence
Nondepolarizing NMBAs function as competitive antagonists intubation (0.8 to 1.2 mg per kg), although, even with large
and inhibit ACh binding to postsynaptic nAChRs on the mo- doses, the onset of action is slower as compared to succinyl-
tor end plate. They are categorized into two classes on the ba- choline [9]. Rocuronium is primarily eliminated in the liver and
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 25: Therapeutic Paralysis 221

TA B L E 2 5 . 1
PHARMACOKINETIC AND PHARMACODYNAMIC PRINCIPLES OF NONDEPOLARIZING NEUROMUSCULAR
BLOCKERSa

Benzylisoquinolinium agents

Cisatracurium (Nimbex) Atracurium (Tracrium) Doxacurium (Nuromax)

Introduced 1996 1983 1991


95% Effective dose (mg/kg) 0.05 0.25 0.0250.030
Initial dose (mg/kg) 0.10.2 0.40.5 Up to 0.1
Onset (min) 23 35 510
Duration (min) 4560 2535 120150
Half-life (min) 2231 20 70100
Infusion dose (g/kg/min) 2.53.0 412 0.30.5
Recovery (min) 90 4060 120180
% Renal excretion Hofmann elimination 510 (Hofmann elimination) 70
Renal failure No change No change Effect
% Biliary excretion Hofmann elimination Minimal Unclear
Hepatic failure Minimal to no change Minimal to no change ?
Active metabolites None, but laudanosine None, but laudanosine ?
Histamine hypotension No Dose-dependent No
Vagal block tachycardia No No No
Ganglionic block hypotension No Minimal to none No
Prolonged block reported Rare Rare Yes

Aminosteroidal agents

Pancuronium Vecuronium Pipecuronium Rocuronium


(Pavulon) (Norcuron) (Arduan) (Zemuron)
Introduced 1972 1984 1991 1994
95% Effective dose (mg/kg) 0.07 0.05 0.05 0.30
Initial dose (mg/kg) 0.1 0.1 0.0850.100 0.61.0
Onset (min) 23 34 5 12
Duration (min) 90100 3545 90100 30
Half-life (min) 120 3080 100
Infusion dose (g/kg/min) 12 12 0.52.0 1012
Recovery (min) 120180 4560 55160 2030
% Renal excretion 4570 50 50+ 33
Renal failure Effect Effect Duration Minimal
% Biliary excretion 1015 3550 Minimal <75
Hepatic failure Mild effect Mild effect Minimal Moderate
Active metabolites 3-OH and 17-OH 3-desacetyl None None
pancuronium vecuronium
Histamine hypotension No No No No
Vagal block tachycardia Modest to marked No No At high doses
Ganglionic block hypotension No No No No
Prolonged ICU block Yes Yes No No

, increased; ICU, intensive care unit.


a
Modified from Grenvik A, Ayres SM, Holbrook PR, et al: Textbook of Critical Care. 4th ed. Philadelphia, WB Saunders, 2000; Watling SM, Dasta JF:
Prolonged paralysis in intensive care unit patients after the use of neuromuscular blocking agents: a review of the literature. Crit Care Med 22(5):884,
1994.

bile. Hepatic or renal dysfunction may reduce drug clearance desacetyl vecuronium, with 50% to 70% activity of the parent
and prolong recovery time. drug. Both vecuronium and its active metabolites are renally ex-
creted. There is potential for prolonged neuromuscular paraly-
sis in patients with renal dysfunction receiving vecuronium by
Vecuronium continuous infusion [10].

An initial intravenous bolus dose of 0.1 mg per kg of vecuro-


nium typically results in neuromuscular paralysis within 3 to Pancuronium
4 minutes and lasts for 35 to 45 minutes. Vecuronium lacks
vagolytic effects, such as tachycardia and hypertension, and Pancuronium is a long-acting nondepolarizing agent that is
produces negligible histamine release. Hepatic metabolism pro- structurally similar to vecuronium. Unique features of pan-
duces three active metabolites, the most significant being 3- curonium are its vagolytic and sympathomimetic activities and
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222 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

potential to induce tachycardia, hypertension, and increased also equally safe when compared with placebo and neostigmine
cardiac output. Pancuronium is primarily excreted unchanged [19].
(60% to 70%) in the urine and bile, whereas the remaining
30% to 40% is hydroxylated by the liver to 3-hydroxy pan-
curonium. It has 50% activity of the parent drug and is renally DRUG INTERACTIONS
eliminated. Renal dysfunction may result in the accumulation
of pancuronium and its metabolites [11]. A substantial number of medications commonly used in clin-
ical practice have the potential for interaction with NMBAs.
These interactions typically influence the degree and duration
Doxacurium of clinical effects through either potentiation of or resistance
to neuromuscular blockade. The most clinically relevant drug
Doxacurium is the most potent nondepolarizing agent avail- interactions with NMBA are discussed here and summarized
able, but it has the slowest onset (as long as 10 minutes). in Table 25.2.
It is practically devoid of histaminergic, vagolytic, or sym- Aminoglycosides and other antibiotics (e.g., tetracyclines,
pathomimetic effects. Doxacurium undergoes minimal hepatic clindamycin, and vancomycin) have the ability to potentiate
metabolism, and excretion occurs unchanged in both the urine neuromuscular blockade and prolong the action of nondepo-
and the bile, with significantly prolonged effects seen in pa- larizing agents through mechanisms including the inhibition
tients with renal dysfunction and, to a lesser extent, hepatic of presynaptic ACh release, reduction of postsynaptic recep-
disease [12,13]. tor sensitivity to ACh, blockade of cholinergic receptors, and
impairment of ion channels. Penicillin and cephalosporin an-
tibiotics do not interact with NMBAs and thus do not influence
the degree of neuromuscular blockade.
Pipecuronium Local, inhalational, and intravenous anesthetic and sedative
agents may potentiate neuromuscular blockade. Local anes-
Pipecuronium is structurally related to pancuronium and its thetics reduce ACh release and decrease muscle contractions
duration of action is 90 to 100 minutes, making it the longest through direct membrane effects, whereas inhalational anes-
acting NMBA. It is metabolized to 3-desacetyl pipecuronium thetics desensitize the postsynaptic membrane and also depress
by the liver, and both the parent compound and the metabo- muscle contractility.
lite are renally excreted. When compared with pancuronium, Cardiovascular drugs such as furosemide, procainamide,
pipecuronium has a longer duration of action, less histamine quinidine, beta-blockers, and calcium channel blockers have
release, and minimal cardiovascular effects [14]. the ability to potentiate neuromuscular blocking effects. The
role of the calcium ion in the release of ACh from vesicles into
the synapse has been well established, although the exact inter-
REVERSAL AGENTS action between calcium channel blockers and NMBAs remains
to be determined. Verapamil, a calcium channel blocker, has
The clinical effects of nondepolarizing neuromuscular block- local analgesic effects and direct skeletal muscle effects, but
ers can be reversed by acetylcholinesterase inhibitors (anti- its significance in drug interaction with NMBAs remains to be
cholinesterases). These agents increase the synaptic concentra- defined.
tion of ACh by preventing its synaptic degradation and allow Chronic antiepileptic therapy, specifically phenytoin and
it to competitively displace nondepolarizing NMBAs from carbamazepine, can increase the resistance to neuromuscular
postsynaptic nAChRs on the motor end plate. Because an- blocking effects, whereas the acute administration of pheny-
ticholinesterase drugs (e.g., neostigmine, edrophonium, and toin potentiates neuromuscular blockade. Chronic phenytoin
pyridostigmine) also inhibit acetylcholinesterase at muscarinic therapy appears to induce an upregulation of ACh receptors,
receptor sites, they are used in combination with the antimus- resulting in decreased postsynaptic sensitivity. Carbamazepine
carinic agents (e.g., atropine or glycopyrrolate) to minimize has been shown to induce resistance and shorten recovery times
adverse muscarinic effects (e.g., bradycardia, excessive secre- in combination with both pancuronium and vecuronium, pos-
tions, and bronchospasm) while maximizing nicotinic effects. sibly resulting from competition at the NMJ [4,20].
Typical combinations include neostigmine and glycopyrrolate
(slower acting agents) and edrophonium and atropine (faster
acting agents). The depth of neuromuscular blockade deter- MONITORING OF NMBAS
mines how rapidly neuromuscular activity returns [15,16].
Sugammadex is a new and novel agent (modified - Current guidelines recommend the routine monitoring of depth
cyclodextrin) that reverses rocuronium and other aminosteroid of neuromuscular blockade in critically ill patients [1]. It is
NMBAs by selectively binding and encapsulating the NMBA important to remember that NMBAs have no analgesic and
[16]. One of the advantages of sugammadex is the rapid re- sedative effect. Careful clinical monitoring of the patient for
versal of the profound neuromuscular block, induced by the signs consistent with inadequate sedation or analgesiasuch as
high dose of rocuronium needed for the rapid-sequence induc- tachycardia, hypertension, salivation, and lacrimationwhile
tion [17,18]an effect that is equivalent to, if not better than, receiving NMBAs is important. A recommendation to use mon-
the spontaneous recovery from succinylcholine. Hence, rocuro- itors such as the Bispectral Index or the Patient State Index
nium/sugammadex may prove to be an effective and safer al- to ensure adequate depth of sedation while receiving NMBAs
ternative to succinylcholine in cases of the difficult airway and seems plausible; however, more studies are needed to determine
contraindications to the use of succinylcholine. Sugammadex whether these monitors are reliable and cost-effective in the
is also useful as a reversal agent whenever the blockade is pro- critical care setting and whether they contribute to improved
found and there is an advantage for a timely reversal [18]. It outcomes [2123]. The modality of choice to monitor the depth
is approved for use in Europe, but not in the United States. of nondepolarizing neuromuscular blockade at present is train-
The nonapproval of the Food and Drug Administration (FDA) of-four (TOF) monitoring. To determine the depth of block-
was based on concerns related to hypersensitivity and allergic ade, four supramaximal stimuli are applied to a peripheral
reactions. However, a recently published Cochrane systemic re- nerve (ideally, the ulnar nerve to assess an evoked response
view concluded that sugammadex was not only effective but of the adductor pollicis muscle) every 0.5 seconds (2 Hz). Each
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Chapter 25: Therapeutic Paralysis 223

TA B L E 2 5 . 2
DRUG INTERACTIONS WITH NEUROMUSCULAR BLOCKING AGENTSa

Therapeutic agent Potential interaction

Antibiotics
Aminoglycosides Potentiate blockade; decreased acetylcholine release
Tetracyclines Potentiate blockade
Clindamycin and lincomycin Potentiate blockade
Vancomycin Potentiate blockade
Sedative/anesthetics Potentiate blockade
Cardiovascular agents
Furosemide Low doses: potentiate blockade; high doses:
antagonize blockade
Beta-blockers Potentiate blockade
Procainamide Potentiate blockade
Quinidine Potentiate blockade
Calcium channel blockers Potentiate blockade
Methylxanthines Antagonize blockade
Antiepileptic drugs Acute: potentiate blockade; chronic: resistance to blockade
Phenytoin
Carbamazepine Resistance to blockade
Ranitidine Antagonize blockade
Lithium Potentiate blockade
Immunosuppressive agents
Azathioprine Mild antagonism; phosphodiesterase inhibition
Cyclosporin Potentiate blockade
Corticosteroids Potentiate steroid myopathy
Local anesthetics Potentiate blockade
a
Adapted from Buck ML, Reed MD: Use of nondepolarizing neuromuscular blocking agents in
mechanically ventilated patients. Clin Pharm 10(1):32, 1991.

stimulus in the train causes the muscle to contract, and fade viously outlined, immature receptors are not confined to the
in the response provides the basis for evaluation. To obtain NMJ proper, but can be found over the entire surface of skele-
the TOF ratio, the amplitude of the fourth response is divided tal muscle (Fig. 25.1). This will lead to increased sensitivity
by the amplitude of the first response. Before administration to depolarizing NMBAs and decreased sensitivity to nondepo-
of a nondepolarizing muscle relaxant, all four responses are larizing NMBAs. Furthermore, these changes in receptor dis-
ideally the same: the TOF ratio is 1 to 1. During a partial non- tribution and physiology put the patient at a heightened risk
depolarizing block, the ratio decreases (fades) and is inversely for succinylcholine-induced hyperkalemia. This is based on the
proportional to the degree of blockade [24]. fact that immature (fetal) and 7nAChRs are low conductance
Three prospective clinical trials have examined the ques- channels with prolonged opening times and significantly higher
tion whether the routine use of TOF monitoring in the ICU potassium efflux into the systemic circulation as compared to
will increase the cost-effectiveness and decrease the incidence mature (adult) nAChRs. Furthermore, succinylcholine is me-
of prolonged neuromuscular weakness. TOF monitoring for tabolized more slowly as compared to ACh, thus prolonging
vecuronium appears to improve the outcome and decrease the the open state of the immature receptors. Upregulation of
cost of therapy. However, these outcomes could not be demon- receptors during periods of immobilization has been described
strated for the benzylisoquinolinium agents, atracurium, and as early as 6 to 12 hours into the disease process. Therefore,
cisatracurium [2527]. it seems advisable to avoid succinylcholine in critically ill pa-
tients beyond 48 to 72 hours of immobilization and/or dener-
vation. In contrast, a reduction in the number of postsynaptic
ADVERSE EFFECTS OF nAChRs will result in resistance to depolarizing and increased
sensitivity to nondepolarizing NMBAs. For conditions asso-
DEPOLARIZING AND ciated with the potential for ACh receptor upregulation, see
NONDEPOLARIZING NMBAS IN Table 25.3.
CRITICALLY ILL PATIENTS
Significant progress has been made in the recent past in our INTENSIVE CARE
understanding of the changes in regulation and distribution of UNITACQUIRED WEAKNESS
ACh receptors during a course of critical illness. The major-
ity of patients hospitalized in an ICU will undergo postsynap- ICU-acquired weakness (ICUAW) is a relatively new term used
tic upregulation of nAChRs due to immobility, upper and/or to describe all weaknesses developed in critically ill patients
lower motor neuron lesions, and/or pharmacologic denerva- after the onset of illness and in the absence of any identi-
tion (such as NMBAs and aminoglycoside antibiotics). As pre- fiable causes. ICUAW is further classified into three entities:
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224 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

FIGURE 25.1. Schematic of the suc-


cinylcholine (SCh)-induced potassium
release in an innervated (top) and den-
ervated (bottom) muscle. In the inner-
vated muscle, the systemically admin-
istered SCh reaches all of the muscle
membrane, but depolarizes only the
junctional (1, 1, , ) receptors be-
cause acetylcholine receptors (AChRs)
are located only in this area. With den-
ervation, the muscle (nuclei) expresses
not only extrajunctional (1, 1, , )
AChRs, but also 7AChRs through-
out the muscle membrane. Systemic
succinylcholine, in contrast to acetyl-
choline released locally, can depolarize
all of the upregulated AChRs, lead-
ing to massive efflux of intracellular
potassium into the circulation, result-
ing in hyperkalemia. The metabolite
of SCh, choline, and possibly succinyl-
monocholine can maintain this de-
polarization via 7AChRs, enhancing
the potassium release and maintain-
ing the hyperkalemia. [From Martyn
JA, Richtsfeld M. Succinylcholine-
induced hyperkalemia in acquired
pathologic states: etiologic factors and
molecular mechanisms. Anesthesiol-
ogy 104:158, 2006, with permission.]

critical illness polyneuropathy (CIP), critical illness myopathy risk of myopathy [31]. Furthermore, both methylprednisolone
(CIM), and critical illness neuromyopathy (CINM) [28,29] (See and hydrocortisone antagonize nAChRs, possibly potentiating
Chapter 180). These conditions occur in up to 50% to 70% the effects of NMBAs [32]. A differential diagnosis of weakness
of patients meeting diagnostic criteria for the systemic inflam- in ICU patients is presented in Table 25.4.
matory response syndrome as well as in patients immobilized
and on mechanical ventilation for more than a week [30]. They
manifest as limb weakness and difficulty in weaning from the Critical Illness Polyneuropathy
mechanical ventilator. Nondepolarizing muscle relaxants of
both classes, aminosteroids and benzylisoquinoliniums, have Electrophysiologic findings of CIP are consistent with a pri-
been associated with the development of these neuromuscular mary, axonal degeneration, resulting in reduction in ampli-
disorders [31]; however, the etiology appears to be multifacto- tudes of the compound muscle action potential and sensory
rial and includes alterations in microvascular blood flow in con-
ditions of sepsis/systemic inflammatory response syndrome and
TA B L E 2 5 . 4
the concomitant administration of corticosteroids [30]. There
is evidence suggesting that high-dose corticosteroids have di- WEAKNESS IN INTENSIVE CARE UNIT PATIENTS:
rect physiologic effects on muscle fibers, resulting in a typical ETIOLOGIES AND SYNDROMESa
myopathy with loss of thick-filament proteins. Atrophy and
weakness are observed primarily in muscles of trunk and ex- Prolonged recovery from neuromuscular blocking agents
tremities, and functional denervation of muscle with NMBAs in (secondary to parent drug, drug metabolite, or
conjunction with corticosteroid therapy seems to heighten the drugdrug interaction)
Myasthenia gravis
EatonLambert syndrome
TA B L E 2 5 . 3 Muscular dystrophy
GuillainBarre syndrome
CONDITIONS ASSOCIATED WITH THE POTENTIAL Central nervous system injury or lesion
FOR NICOTINIC ACETYLCHOLINE RECEPTOR Spinal cord injury
UPREGULATION Steroid myopathy
Mitochondrial myopathy
Severe infection/SIRS Human immunodeficiency virusrelated myopathy
Muscle atrophy associated with prolonged immobility Critical illness myopathy
Thermal injury Disuse atrophy
Upper and/or lower motor neuron defect Critical illness polyneuropathy
Prolonged pharmacologic or chemical denervation Severe electrolyte toxicity (e.g., hypermagnesemia)
(e.g., NMBAs, magnesium, aminoglycoside antibiotics, Severe electrolyte deficiency (e.g., hypophosphatemia)
and clostridial toxins)
a
Adapted from Murray MJ, Cowen J, DeBlock H, et al: Clinical
NMBAs, neuromuscular blocking agents; SIRS, systemic inflammatory practice guidelines for sustained neuromuscular blockade in the adult
response syndrome. critically ill patient. Crit Care Med 30(1):142, 2002, with permission.
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Chapter 25: Therapeutic Paralysis 225

TA B L E 2 5 . 5
RECOMMENDATIONS FOR ADMINISTRATION OF NEUROMUSCULAR BLOCKING AGENTS (NMBAS)
TO ICU PATIENTSa

1. Develop, use, and document a standardized approach for administering and monitoring NMBA
2. Use NMBA only after optimizing ventilator settings and sedative and analgesic medication administration
3. Establish the indications and clinical goals of neuromuscular blockade, and evaluate at least daily
4. Select the best NMBA on the basis of patient characteristics:
A. Use intermittent NMBA therapy with pancuronium, doxacurium, or other suitable agent if clinical goals can be met
B. If continuous infusion is required and renal or hepatic dysfunction is present, select atracurium or cisatracurium, and avoid
vecuronium
5. Use the lowest effective dose for the shortest possible time (<48 h if possible), particularly if corticosteroids are concomitantly
administered
6. Administer adequate analgesic and/or sedative medication during neuromuscular blockade, and monitor clinically and by
bispectral array EEG if available
7. Systematically anticipate and prevent complications, including provision of eye care, careful positioning, physical therapy, and
DVT prophylaxis
8. Avoid the use of medications that affect NMBA actions. Promptly recognize and manage conditions that affect NMBA actions
9. Adjust NMBA dosage to achieve clinical goals (i.e., patientventilator synchrony, apnea, or complete paralysis)
10. Periodically (i.e., at least once or twice daily) perform NMBA dosage reduction, and preferably cessation (drug holiday) if clinically
tolerated, to determine whether neuromuscular blockade is still needed and to perform physical and neurologic examination
11. Periodically perform and document a clinical assessment in which spontaneous respiration, as well as limb movement, and/or
the presence of DTRs are observed during steady-state infusion and/or during dosage reduction/cessation. With deep blockade,
muscle activity may be present only during dosage reduction/cessation
12. Perform and document scheduled (i.e., every 48 h) TOF testing for patients receiving vecuronium NMBA and/or undergoing
deep neuromuscular blockade (i.e., apnea or complete paralysis), and adjust dosage to achieve one-fourth or more twitches.
If clinical goals cannot be met when one-fourth or more twitches are present during steady-state infusion, demonstrate
one-fourth or more twitches during dosage reduction/cessation. Consider TOF testing in all patients

DTR, deep tendon reflexes; DVT, deep venous thrombosis; EEG, electroencephalogram; TOF, train of four.
a
Modified from Gehr LC, Sessler CN: Neuromuscular blockade in the intensive care unit. Semin Respir Crit Care Med 22:175, 2001, with permission.

nerve action potential. Although several case reports have sug- ICU and hospital mortality in critically ill patients, CIP and
gested that NMBAs are causative agents in the etiology of this CIM appear to be important causes of increased morbidity dur-
disorder, prospective studies of CIP have not confirmed a cor- ing and after acute care hospital stay [37] (See Chapter 180).
relation between the use of NMBAs, steroids, and CIP [33].
It seems plausible, however, that NMBAs contribute to nerve
and muscle damage during a course of critical illness. Their
use should be avoided whenever possible until more prospec- SUMMARY AND
tive data demonstrating their safety in critically ill patients are RECOMMENDATIONS
available [34] (See Chapter 180).
Although there is currently insufficient evidence to demonstrate
an unequivocal link between the use of NMBAs and an increase
in morbidity and mortality in critically ill patients, it seems
Critical Illness Myopathy prudent to perform a careful riskbenefit analysis prior to the
administration of this class of drugs in the ICU setting. Indeed,
CIM can occur in association with, or independently from, a recent prospective, randomized study of patients in the early
CIP. A group of several myopathies of critical illness are now stage of the acute respiratory distress syndrome demonstrated
thought to be part of the same syndrome; these include acute that use of cisatracurium was associated with improved sur-
quadriplegic myopathy, critical care myopathy, acute corti- vival without an increase in ICUAW [38]. Nonetheless, more
costeroid myopathy, acute hydrocortisone myopathy, acute prospective data are needed to identify proper indications, se-
myopathy in severe asthma, and acute corticosteroid and lection of agents, and doses in the ICU setting. Concomitant use
pancuronium-associated myopathy [35]. The major feature of of drugs predisposing patients for the development of CIM-like
this syndrome is flaccid, diffuse weakness, involving all limb steroids and aminoglycoside antibiotics should alert the clini-
muscles and neck flexors, and often the facial muscles and di- cian for the increased risk of CIP/CIM in this setting. Succinyl-
aphragm. As with CIP, this can result in difficulty to wean from choline can subject patients who are immobilized with upper
the mechanical ventilator. The syndrome is more difficult to and lower motor neuron lesions or with burns to a markedly
diagnose than CIP, and diagnostic evaluations include electro- increased risk for succinylcholine-induced hyperkalemia, and
physiologic studies, muscle biopsy, and laboratory evaluations should be avoided in the ICU whenever possible. For recom-
(plasma creatine kinase levels). Again, there is no definitive ev- mendations for the administration of NMBAs to ICU patients,
idence suggesting that NMBAs are causative agents for this please see Table 25.5.
syndrome, but rather a component in a multifactorial etiology.
However, the incidence of CIP and CIM appears to be higher
in ICUs where these agents are more frequently used [36]. ACKNOWLEDGMENTS
The question whether CIP and CIM increase hospital mor-
tality was recently addressed by Latronico et al. [37]. Although We thank Dr. Jerry D. Thomas and Dr. Greg A. Bauer for the
only limited data are available suggesting that CIP increases significant contributions to previous revisions of this chapter.
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226 Section I: Procedures, Techniques, and Minimally Invasive Monitoring

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SECTION II MINIMALLY INVASIVE


MONITORING
ALAN LISBON

CHAPTER 26 ROUTINE MONITORING OF


CRITICALLY ILL PATIENTS
PATRICK TROY, NICHOLAS A. SMYRNIOS AND MICHAEL D. HOWELL

A key difference between intensive care units (ICUs) and other of this vital measurement. Clinicians should understand the im-
hospital units is the level of detail with which patients are rou- pact of the thermometer type and the measurement site on how
tinely monitored. This careful monitoring alerts the health care to interpret the patients reported temperature.
team to changes in the patients severity of illnesshelping to
both diagnose disease and assess prognosis. Careful monitor-
ing also helps the health care team safely apply therapies such
as volume resuscitation, vasoactive infusions, and mechanical Indications for Temperature Monitoring
ventilation.
The Society of Critical Care Medicines Task Force on Guide-
This chapter deals with the routine, predominantly nonin-
lines recommendations for care in a critical care setting grades
vasive monitoring that is often done for many patients in ICUs.
temperature monitoring as an essential service for all criti-
It examines the indications for, the technology of, and problems
cal care units [3]. Critically ill patients are at high risk for
encountered in the routine monitoring of temperature, blood
temperature disorders because of debility, impaired control of
pressure, ECG rhythm, ST segments, respiratory rate, and oxy-
temperature, frequent use of sedative drugs, and a high pre-
gen and carbon dioxide levels. In addition, it reviews noninva-
disposition to infection. All critically ill patients should have
sive monitoring of tissue perfusion, with particular attention to
core temperature measured at least intermittently. Patients with
gastric tonometry, sublingual capnometry, and transcutaneous
marked temperature abnormalities should be considered for
oxygen and carbon dioxide monitoring.
continuous monitoring; patients undergoing active interven-
tions to alter temperature, such as breathing heated air or using
a coolingwarming blanket, should have continuous monitor-
MONITORING SYSTEMS ing to prevent overtreatment or undertreatment of temperature
disorders.
When ICUs came into being in the late 1950s, nurses moni-
tored patients vital signs intermittently. Continuous measure-
ment was either unavailable or necessitated invasive proce-
dures. Now, however, nearly all routine vital signs can now Measurement Sites
be monitored accurately, noninvasively, and continuously. As
The goal of temperature measurements is generally to estimate
a result, patients now are monitored more intensively and con-
core temperaturethe deep body temperature that is carefully
tinuously in the ICU than in any other part of the hospital, with
regulated by the hypothalamus so as to be independent of tran-
the possible exception of the operating room.
sient small changes in ambient temperature. Core temperature
Over the past decades, the trend in monitoring systems has
exists more as a physiologic concept than as the temperature
been toward multipurpose systems that integrate monitoring
of an anatomic location. An ideal measurement site would be
of a variety of parameters. Multipurpose systems eliminate the
protected from heat loss, painless and convenient to use, and
need for multiple, freestanding devicesreducing clutter and
would not interfere with the patients ability to move and com-
improving workflow ergonomics at the bedside. These systems
municate. No one location provides an accurate measurement
also interface critical care information systems to provide more
of core temperature in all clinical circumstances.
efficient data management, quality improvement reports, and
in some cases prospective data-driven alerts.
Sublingual Temperature Measurements
Sublingual temperature measurements are convenient, but suf-
TEMPERATURE MONITORING fer numerous limitations. Although open-mouth versus closed-
mouth breathing and use of nasogastric tubes do not alter
Temperature changes in the critically ill are associated with temperature measurement [4], oral temperature is obviously
significant morbidity and mortality [1] (see Chapters 65 and altered if measured immediately after the patient has consumed
66)making it clinically important to recognize an abnormal hot or cold drinks. Falsely low oral temperatures may occur
temperature. In one surgical ICU study, rectal temperatures on because of cooling from tachypnea. Sixty percent of sublin-
admission were normal in only 30% of patients, were above gual temperatures are more than 1 F lower than simultane-
37.6 C in 38%, and were below 36.8 C in 32% [2]. An ab- ously measured rectal temperatures; 53% differ by 1 to 2 F,
normal temperature is frequently the earliest clinical sign of and 6% differ by more than 2 F. Continuous sublingual mea-
infection, inflammation, central nervous system dysfunction, surement is not generally practical. Sublingual measurement is
or drug toxicity. Unfortunately, the type of thermometer and best suited for intermittent monitoring when some inaccuracy
the site where the temperature is taken can affect the accuracy can be tolerated.

227
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228 Section II: Minimally Invasive Monitoring

Axillary Temperature Measurements great vessel and rectal temperatures [7,8]. Bladder temperature
under steady-state conditions is more reproducible than that
Axillary temperatures are commonly used as an index of core
taken at most other sites [7].
temperature. Although some studies indicate close approxima-
tion of the axillary site with pulmonary artery temperatures
[5], temperatures average 1.5 to 1.9 C lower than tympanic Central Circulation Temperature Measurements
temperatures [6]. Positioning the sensor over the axillary artery
may improve accuracy. The accuracy and precision of axillary ICU practitioners can measure the temperature of blood in
temperature measurements are less than at other sites [6], per- the pulmonary artery using a thermistor-equipped pulmonary
haps due in part to the difficulty of maintaining a good probe artery catheter. The temperature sensor is located at the distal
position. tip and can record accurate great vessel temperatures once the
catheter is in place in the pulmonary artery. Pulmonary artery
temperatures have generally been accepted as the gold standard
Rectal Temperature Measurements for accurate measures of core temperature, although readings
Rectal temperature is the most widely accepted standard of might be expected to differ from core temperature when heated
measuring core temperature in clinical use. Before a rectal ther- air was breathed or warm or cold intravenous fluids were in-
mometer is inserted, a digital rectal examination should be fused. However, this understanding may not be true in neuro-
performed because feces can blunt temperature measurement. surgical patients. A study in patients undergoing neurosurgical
Readings are more accurate when the sensor is passed more procedures with induced hypothermic circulatory arrest found
than 10 cm (4 in) into the rectum. Rectal temperature correlates that pulmonary arterial temperature measurement was not ef-
well in most patients with distal esophageal, bladder, and tym- fective in assessing core brain temperature with a correlation
panic temperatures [7]. Rectal temperatures typically respond coefficient of 0.63. A greater degree of correlation was found in
to induced changes in temperature more slowly than other cen- bladder temperature [15]. Inserting a central venous thermistor
tral measurement sites [8]. Reusable, electronic, sheath-covered specifically to monitor temperature is probably warranted only
rectal thermometers have been associated with the transmission when other sites are felt to be unreliable and accurate, rapid,
of Clostridium difficile and vancomycin-resistant Enterococ- continuous temperature measurements are critical to the pa-
cus, so disposable probes are generally preferred. tients management.

Esophageal Temperature Measurements


Esophageal temperature is usually measured with an electric, Types of Thermometers
flexible temperature sensor. On average, esophageal tempera-
tures are 0.6 C lower than rectal temperatures [9]. However, Mercury Thermometers
the measured temperature can vary greatly depending on the
position of the sensor in the esophagus. In the proximal esoph- Although mercury thermometers were historically been the
agus, temperature is influenced by ambient air [10]. During most common type in clinical use, environmental and health
hypothermia, temperatures in different portions of the esoph- concerns related to mercury have resulted in several state and
agus may differ by up to 6 C [10]. Because of the proximity local legislative efforts to phase out this type of thermometer.
of the distal esophagus to the great vessels and heart, the dis- Mercury and other liquidexpansion-based thermometers can
tal esophageal temperature responds rapidly to changes in core give a falsely low measurement when the thermometer is left
temperature [11]. Changes in esophageal temperature may in- in place for too short a period; falsely high temperatures result
accurately reflect changes in core temperature when induced from failure to shake the mercury down.
temperature change occurs because of the inspiration of heated
air, gastric lavage, or cardiac bypass or assist [11]. Liquid Crystal Display Thermometers
Tympanic Temperature Measurements Liquid crystal display (LCD) thermometers contain liquid crys-
tals embedded in thin adhesive strips that are directly attached
Health care providers can measure tympanic temperature with to the patients skin. LCD thermometers are most commonly
specifically designed thermometers that are commonly used in applied to the forehead for ease of use and steady perfusion,
the ICU. However, several studies have demonstrated poor cor- but can be applied to any area of the skin. Like all skin temper-
relation with ICU patients core temperatures [12,13]. Accu- ature measurements, they may poorly reflect core temperature
racy depends in part on operator experiencebut even when when the skin is hypoperfused or patients have vasomotor in-
trained, experienced ICU nurses use tympanic thermometers, stability. Forehead skin temperature is typically lower than core
the variability in repeated measurements was more than 0.5 F temperatures by 2.2 C [16], and changes in LCD forehead tem-
in 20% of patients [14]. Unlike temporal artery measurements, perature lag behind changes in core temperature by more than
which are not known to have complications, tympanic temper- 12 minutes [17]. LCD skin thermometry is probably best used
ature measurements come with some risk. Perforation of the in patients with stable, normal hemodynamics who are not ex-
tympanic membrane and bleeding from the external canal due pected to experience major temperature shifts and in whom
to trauma from the probe have been reported. the trend of temperature change is more important than the
accuracy of the measurement.
Temporal Artery Measurements
Temporal artery measurements are not known to have compli- Standard Digital Thermometers:
cations. Their accuracy is reviewed later. Thermocouples and Thermistors
Electric thermometers convert an electrical temperature signal
Urinary Bladder Temperature Measurements
into digital displays, frequently by use of thermocouples and
Providers can easily measure the urinary bladder temperature thermistors as probes. Thermocouples and thermistors can be
with a specially designed temperature probe embedded in a fashioned into thin wires and embedded in flexible probes that
Foley catheter [68]. In patients undergoing induced hypother- are suitable for placing in body cavities to measure deep tem-
mia and rewarming, bladder temperatures correlate well with perature.
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Chapter 26: Routine Monitoring of Critically Ill Patients 229

Thermocouples consist of a junction of two dissimilar met- changes in probe position can affect the accuracy of esophageal
als. The voltage change across the junction can be precisely measurements, so this mode is probably best used in patients
related to temperature. The measuring thermocouple must be undergoing active, aggressive temperature management in cen-
calibrated against a second constant-temperature junction for ters with substantial experience with the modality. Meanwhile,
absolute temperature measurements. In the range of 20 to rectal probes may be extruded or may be refused by patients.
50 C, thermocouples may have a linearity error of less than The third option, bladder temperature monitoring, is simplified
0.1 [18]. by the fact that most critically ill patients have an indwelling
Thermistors consist of semiconductor metal oxides in which Foley catheter. Monitoring the bladder temperature in these
the electrical resistance changes inversely with temperature. A patients requires only a thermistor-equipped catheter. Patients
linearity error of up to 4 C may occur over the temperature with a thermistor-tipped pulmonary artery catheter already in
range of 20 to 50 C, but this can be substantially reduced place require no additional temperature monitoring.
by mathematical adjustments and electrical engineering tech-
niques [18]. Semiconductors measure temperature by taking Patient Safety and Temperature Monitoring
advantage of the fact that the base-to-emitter voltage change is
temperature dependent, whereas the collector current of the sil- Therapeutic hypothermia is increasingly prevalent in ICU set-
icon resistor is constant. Thermistors are more sensitive, faster tings (Chapter 65]). Some devices used to induce hypothermia
responding, and less linear than thermocouples or semiconduc- are closed-looped systems. Since core temperature probes can
tors [18]. fail (for example, dislodgement of a rectal probe to a position
outside the patient), practitioners should consider monitoring
Infrared Emission Detection Thermometers core temperature from two sites when temperature is being
actively manipulated.
Tympanic Thermometers. Commonly used in a hospital set-
ting, infrared emission detection tympanic thermometers use
a sensor that detects infrared energy emitted by the core-
temperature tissues behind the tympanic membrane. Infrared
ARTERIAL BLOOD PRESSURE
emissions through the tympanic membrane vary linearly with MONITORING
temperature. Operator technique is important: errors due to
improper calibration, setup, or poor probe positioning can sig- The first recorded blood pressure measurement occurred in
nificantly alter temperatures [19]. Measurements are most ac- 1733 andsomewhat surprisinglywas intra-arterial pres-
curate when the measuring probe blocks the entrance of ambi- sure monitoring. The Reverend Stephen Hales placed a 9-foot
ent air into the ear canal and when the midposterior external brass tube in a horses crural artery and found a blood pressure
ear is tugged posterosuperiorly so as to direct the probe to the of about 8 feet 3 inches. This was obviously not clinically ap-
anterior, inferior third of the tympanic membrane. Studies are plicable. In the mid-1800s, Carl Ludwig recorded the first arte-
mixed on whether tympanic thermometers provide accurate rial pressure waveforms, but it was not until 1881 that the first
core temperature measurements, ranging from a 4% clinically noninvasive blood pressure recordings were made. In 1896,
meaningful error rate [14] to a finding that 21% of tympanic Riva-Rocci developed and popularized the mercury sphygmo-
readings might result in delays in therapy for or evaluation of manometer, which was then adopted and disseminated at least
fever [20]. in part by Harvey Cushing. In 1905, Korotkoff developed tech-
niques for detecting diastolic pressure by listening for what are
Temporal Artery Thermometers. Infrared technology can also now called Korotkoff sounds. More clinical techniques of di-
measure temperature over the temporal artery. A probe is rect blood pressure measurement by intra-arterial cannula were
passed over the forehead and searches for the highest tem- initially developed in the 1930s and popularized in the 1950s
perature; some systems also scan the area behind the ear. An [22]. These measurements were soon accepted as representing
algorithm estimates ambient heat loss and blood cooling to true systolic and diastolic pressures.
calculate core temperature. The device is convenient, pain- Since that time, a variety of invasive and alternative indi-
less, and provides a rapid reading. Although one small study rect methods have been developed that equal and even surpass
of normothermic patients found good correlation with pul- auscultation in reproducibility and ease of measurement. This
monary artery temperatures [5], another study in patients with section examines the advantages and disadvantages of various
a broader temperature range found that 89% of measurements methods of arterial pressure monitoring and provides recom-
differed from pulmonary artery temperatures by more than mendations for their use in the ICU.
0.5 C, the amount the authors had specified a priori as clini-
cally significant [21].
Noninvasive (Indirect) Blood
Pressure Measurement
Selecting the Measurement Site
Providers can indirectly monitor blood pressure using a num-
The site used to monitor temperature must be an individualized ber of techniques, most of which describe the external pressure
choice, but certain generalizations can be made. When inter- applied to block flow to an artery distal to the occlusion. These
mittent temperature measurement is all that is clinically needed methods therefore actually detect blood flow, not intra-arterial
(e.g., in routine monitoring), or the consequences of inaccurate pressure, although one method describes the pressure required
measurement are low, rectal or sublingual measurement may be to maintain a distal artery with a transmural pressure gradi-
preferred. If less accuracy is required, tympanic, temporal, or ent of zero. These differences in what is actually measured are
axillary sites may be chosen. When more accurate measurement the major points of discrepancy between direct and indirect
is needed, bladder, esophageal, and rectal temperatures in gen- measurements.
eral appear to be most accurate and reproduciblealthough Indirectly measured pressures vary depending on the size of
rectal temperatures may lag behind other temperatures when the cuff used. Cuffs of inadequate width and length can pro-
the patients status is changing quickly [7,13]. However, routine vide falsely elevated readings. Bladder width should equal 40%
measurement of esophageal temperatures would necessitate in- and bladder length at least 60% of the circumference of the ex-
serting an esophageal probe in all patients. In addition, small tremity measured [23]. Anyone who makes indirect pressure
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230 Section II: Minimally Invasive Monitoring

measurements must be aware of these factors and carefully cultation. Pulse oximeters have been similarly used and corre-
select the cuff to be used. late well with other methods; the point at which a plethysmo-
graphic trace appears is taken as the systolic pressure [27].

Manual Methods
Automated Methods
Auscultatory (Riva-Rocci) Pressures
Automated indirect blood pressure devices operate on one of
The traditional way to measure blood pressure involves inflat- several principles: Doppler flow, infrasound, oscillometry, vol-
ing a sphygmomanometer cuff around an extremity and aus- ume clamp, arterial tonometry, and pulse wave arrival time.
cultating over an artery distal to the occlusion. Sounds from
the vibrations of the artery under pressure (Korotkoff sounds) Doppler Flow
indicate systolic and diastolic pressures. The level at which the
sound first becomes audible is taken as the systolic pressure. Systems that operate on the Doppler principle take advantage
The point at which there is an abrupt diminution in or disap- of the change in frequency of an echo signal when there is
pearance of sounds is used as diastolic pressure. This method, movement between two objects. Doppler devices emit brief
still commonly used in the ICU, yields an acceptable value in pulses of sound at a high frequency that are reflected back
most situations. Its advantages include low cost, time-honored to the transducer [28]. The compressed artery exhibits a large
reliability, and simplicity. Disadvantages include operator vari- amount of wall motion when flow first appears in the vessel
ability, susceptibility to environmental noise, and the absence distal to the inflated cuff. This causes a change in frequency of
of Korotkoff sounds when pressures are very low. Auscultatory the echo signal, known as a Doppler shift. The first appearance
pressures also correlate poorly with directly measured pres- of flow in the distal artery represents systolic pressure. In an un-
sures at the extremes of pressure [24]. compressed artery, the small amount of motion does not cause
a change in frequency of the reflected signal. Therefore, the
Manual Oscillation Method disappearance of the Doppler shift in the echo signal repre-
sents diastolic pressure [29].
When a cuff is slowly deflated and blood first begins to flow
through the occluded artery, the arterys walls begin to vibrate. Infrasound
This vibration can be detected as an oscillation in pressure
and has served as the basis for the development of several au- Infrasound devices use a microphone to detect low-frequency
tomated blood pressure monitoring devices. However, it also (20 to 30 Hz) sound waves associated with the oscillation of the
continues to be used in manual blood pressure measurement. arterial wall. These sounds are processed by a minicomputer,
The first discontinuity in the needle movement of an aneroid and the processed signals are usually displayed in digital form
manometer indicates the presence of blood flow in the distal [30].
artery and is taken as systolic pressure [25]. The advantages
of the oscillation method are its low cost and simplicity. The Oscillometry
disadvantages include the inability to measure diastolic pres- Oscillometric devices operate on the same principle as manual
sure, poor correlation with directly measured pressures [25], oscillometric measurements. The cuff senses pressure fluctua-
and lack of utility in situations in which Riva-Rocci measure- tions caused by vessel wall oscillations in the presence of pul-
ments are also unobtainable. Aneroid manometers may also satile blood flow [31]. Maximum oscillation is seen at mean
be inaccurate: in one study, 34% of all aneroid manometers in pressure, whereas wall movement greatly decreases below di-
use in one large medical system gave inaccurate measurements, astolic pressure [32]. As with the other automated methods
even when more lenient standards were used than those advo- described, the signals produced by the system are processed
cated by the National Bureau of Standards and the Association electronically and displayed in numeric form.
for the Advancement of Medical Instrumentation [26]. In the
same survey, 36% of the devices were found to be mechanically
Volume Clamp Technique
defectivepointing out the need for regular maintenance. Al-
though the manometers themselves can also be used for auscul- The volume clamp method avoids the use of an arm cuff. A fin-
tatory measurements, oscillometric readings probably provide ger cuff is applied to the proximal or middle phalanx to keep the
no advantage over auscultation in the ICU. artery at a constant size [33]. The pressure in the cuff is changed
as necessary by a servocontrol unit strapped to the wrist. The
Palpation, Doppler, and Pulse-Oximetric Methods feedback in this system is provided by a photoplethysmograph
that estimates arterial size. The pressure needed to keep the
Systolic pressures can be measured any method that detects artery at its unloaded volume can be used to estimate the intra-
flow in a distal artery as the blood pressure cuff is slowly de- arterial pressure [34].
flated. Palpation of the radial artery is the most commonly
used technique; it is most useful in emergency situations in
which Korotkoff sounds cannot be heard and an arterial line is
Arterial Tonometry
not in place. The inability to measure diastolic pressure makes Arterial tonometry provides continuous noninvasive measure-
the palpation method less valuable for ongoing monitoring. ment of arterial pressure, including pressure waveforms. It
In addition, palpation obtains no better correlation with direct slightly compresses the superficial wall of an artery (usually the
measurements than the previously described techniques. In one radial). Pressure tracings obtained in this manner are similar
study, variation from simultaneously obtained direct pressure to intra-arterial tracings. A generalized transfer function can
measurements was as high as 60 mm Hg [24]. Like other indi- convert these tracings to an estimate of aortic pressure [35].
rect methods, palpation tends to underestimate actual values to This method has not yet achieved widespread clinical use. One
greater degrees at higher levels of arterial pressure. Any method available system studied in ICU patients had approximately
which detects blood flow distal to a sphygmomanometer cuff one third of MAP readings which differed by 10 mm Hg
may be used in this fashion. Doppler machines are commonly compared with intra-arterial pressure measurements and was
used and may be particularly useful in situations where the associated with significant drift during the course of the study
pulse is not palpable or environmental noise precludes aus- [36]. However, more studies of a different system reported more
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Chapter 26: Routine Monitoring of Critically Ill Patients 231

accurate readings in patients undergoing anesthesia [37], in- of arterial catheters. Here, we discuss the advantages and dis-
cluding those with induced hypotension [38]. advantages of invasive monitoring compared with noninvasive
means.
Arterial catheters contain a fluid column that transmits
Utility of Noninvasive Blood the pressure back through the tubing to a transducer. A low-
compliance diaphragm in the transducer creates a reproducible
Pressure Measurements volume change in response to the applied pressure change. The
volume change alters the resistance of a Wheatstone bridge and
Only four of the methods described previously (infrasound, is thus converted into an electrical signal. Most systems display
oscillometry, Doppler flow, volume clamp) are associated with the pressure in both wave and numeric forms.
significant clinical experience. Of these, methods that use infra-
sound technology correlate least well with direct measures of
arterial blood pressure [31,39]. Therefore, infrasound is rarely
Problems in Direct Pressure Monitoring
used in systems designed for critical care. System-Related Problems. Several technical problems can af-
Although they have not been consistently accurate, auto- fect the measurement of arterial pressure with the arterial line.
mated methods have the potential to yield pressures as accurate Transducers must be calibrated to zero at the level of the heart.
as values derived by auscultation. Commonly used oscillomet- Improper zeroing can lead to erroneous interpretation. Throm-
ric methods can correlate to within 1 mm Hg of the directly bus formation at the catheter tip can occlude the catheter, mak-
measured group average values [31] but may vary substantially ing accurate measurement impossible. This problem can be
from intra-arterial pressures in individual subjects, particularly largely eliminated by using a 20-gauge polyurethane catheter,
at the extremes of pressure. One study revealed as good a corre- rather than a smaller one, with a slow, continuous heparin flush
lation with directly measured pressures as Riva-Rocci pressures [49], although this may be associated with heparin-induced
have traditionally obtained [31]. Another study demonstrated thrombocytopenia [50]. Because movement may interrupt the
that mean arterial pressures determined by auscultation were column of fluid and prevent accurate measurement, the pa-
extremely close to those measured by automated devices [40]. tients limb should be immobile during readings.
When volume clamp methods using a finger cuff have been The frequency response of the system is a phenomenon not
compared with standard methods [41,42], these devices have only of transducer design but also of the tubing and the fluid
been found to respond rapidly to changes in blood pressure in it. The length, width, and compliance of the tubing all af-
and give excellent correlation in group averages. In one study fect the systems response to change. Small-bore catheters are
looking at a large number of measurements, 95% of all mea- preferable because they minimize the mass of fluid that can os-
surements using this method were within 10 mm Hg of the cillate and amplify the pressure [51]. The compliance of the
directly measured values [43]. Studies by Aitken et al. [42] system (the change in volume of the tubing and the transducer
and Hirschl et al. [41] demonstrated acceptable correlation of for a given change in pressure) should be low [51]. In addi-
volume clamp technique with systolic pressures measured di- tion, bubbles in the tubing can affect measurements in two
rectly. However, other studies have shown clinically significant ways. Large amounts of air in the measurement system damp
differences between the volume clamp technique and invasively the system response and cause the system to underestimate the
measured pressures in patients undergoing anesthesia [44]. pressure [52]. This is usually easily detectable. Small air bub-
One of the proposed advantages of automated noninvasive bles cause an increase in the compliance of the system and can
monitoring is patient safety. Avoiding arterial lines eliminates significantly amplify the reported pressure [51,52].
the risk of vessel occlusion, hemorrhage, and infection. Au-
tomated methods, however, have complications of their own. Arterial Catheter Infections. Recent data challenge the clas-
Ulnar nerve palsies have been reported with frequent inflation sical perception that that arterial catheters are less likely to
and deflation of a cuff [45]. Decreased venous return from the become infected [53] than central venous catheters. A prospec-
limb and eventually reduced perfusion to that extremity can tive cohort study examined 321 arterial and 618 central venous
also be seen when the cuff is set to inflate and deflate every catheters and found that arterial catheter colonization occurred
minute [45,46]. with similar incidence to central venous catheter colonization
In summary, automated noninvasive blood pressure forms [54]. Another recent study found similar results [55]. There
a major component of modern critical care monitoring. Oscil- is good evidence to support a link between the incidence of
lometric and Doppler-based devices are adequate for frequent catheter colonization and catheter related blood stream infec-
blood pressure checks in patients without hemodynamic in- tions [56]. Although one study suggested that full barrier pre-
stability, in patient transport situations in which arterial lines cautions did not reduce the incidence of arterial line infection,
cannot be easily used, and in the severely burned patient, in interpretation of this trial is complex [57]. Taken together, the
whom direct arterial pressure measurement may lead to an un- weight of evidence suggests that arterial catheters are an im-
acceptably high risk of infection [47]. Automated noninvasive portant potential source for infection in the critically ill patient
blood pressure monitors have a role in following trends of pres- and should be treated similar to central venous catheters in this
sure change [48] and when group averages, not individual mea- setting.
surements, are most important. In general, they have significant Finally, the location within the hospital where the procedure
limitations in patients with rapidly fluctuating blood pressures is performed is important as catheters placed in non-ICU loca-
and may diverge substantially from directly measured intra- tions may be associated with an increased risk of colonization
arterial pressures. Given these limitations, critical care practi- versus those placed in the ICU [54].
tioners should be wary of relying solely on these measurements
in patients with rapidly changing hemodynamics or in whom Site Selection. The radial artery is the most common site of ar-
very exact measurements of blood pressure are important. terial cannulation for pressure measurement. This site is acces-
sible and can be easily immobilized to protect both the catheter
and the patient. The major alternative site is the femoral artery.
Direct Invasive Blood Pressure Measurement Both sites are relatively safe for insertion [58,59]. The ulnar,
brachial, dorsalis pedis, and axillary arteries are also used with
Direct blood pressure measurement is performed with an intra- some frequency [60]. Mechanical complications such as bleed-
arterial catheter. Chapter 3 reviews insertion and maintenance ing and nerve injury are discussed in Chapter 11. How should a
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232 Section II: Minimally Invasive Monitoring

provider choose a site? Although there are a number of theoret- either absent or inaccurate, and do not require repeated in-
ical considerations about comparing blood pressures from one flation and deflation of a cuff. In addition, they provide easy
site to another, there is little data in critically ill patients. A sys- access for phlebotomy and blood gas sampling, and they may
tematic review of 19,617 radial, 3,899 femoral, and 1,989 ax- provide additional information about cardiac status. However,
illary cannulations found that serious complications occurred particular care should be taken with aseptic technique and line
infrequently (<1% of cannulations) and were similar between site maintenance, since the reported incidence of arterial line
the sites [60]. In 14 septic surgical patients on vasopressors, infection approaches that of central venous catheterization. Re-
radial pressures were significantly lower than femoral arterial gardless of the method used, the mean arterial pressure should
pressures. In 11 of the 14 patients, vasopressor dose was re- generally be the value used for decision making in most criti-
duced based on the femoral pressure without untoward con- cally ill patients.
sequences; after vasopressors were discontinued, radial and
femoral pressures equalized. The authors concluded that clin-
ical management based on radial artery pressures may lead to ELECTROCARDIOGRAPHIC
excessive vasopressor administration [61]. Similar significant
differences in systolic pressures between the radial and femoral MONITORING
sites were found in the reperfusion phase of liver transplanta-
Almost all ICUs in the United States routinely perform con-
tion, although MAPs did not differ [62]. However, another
tinuous electrocardiographic (ECG) monitoring. Continuous
somewhat larger observational study in critically ill patients
ECG monitoring combines the principles of ECG, which have
[63] found no clinically meaningful differences in blood pres-
been known since 1903, with the principles of biotelemetry,
sures between the sites. Although data are sparse, mean arterial
which were first put into practical application in 1921 [65].
pressure readings between the radial and femoral sites are prob-
Here we review the principles of arrhythmia monitoring, au-
ably interchangeable in many or most patients. There may be
tomated arrhythmia detection, and the role of automated ST
a preference toward using femoral arterial pressure readings
segment analysis.
in patients with vasopressor resistant shock, but this decision
ECG monitoring in most ICUs is done over hard-wired ap-
should be balanced by the risks of the femoral approach.
paratus. Skin electrodes detect cardiac impulses and transform
Should the risk of infection drive site selection? The data
them into an electrical signal, which is transmitted over wires
are mixed. Earlier work suggested that there was no differ-
directly to the signal converter and display unit. This removes
ence in infection rates between the femoral and radial sites
the problems of interference and frequency restrictions seen in
[60]. More recently, a prospective observational study of 2,949
telemetry systems. Although this comes at the cost of reduced
catheters in the intensive care unit found the incidence of
patient mobility, mobility is often not an immediate concern
catheter related blood stream infection was significantly higher
for this group of patients.
for femoral access (1.92/1,000 catheter-days) than for radial
access (0.25/1,000 catheter-days) (odds ratio, 1.9; p = 0.009].
Localized skin infections were also significantly increased in
femoral versus radial arterial catheters. In addition, femoral ar- Arrhythmia Monitoring in the ICU
terial catheter blood stream infections may have an increased
association with gram negative bacteria when compared to The American Heart Associations Practice Standards guideline
the radial site, similar to previous data from central venous considers continuous ECG monitoring a Class I intervention
catheters [64]. for all patients with indications for intensive care, regardless
of whether the patients primary admitting diagnosis related
to a cardiac problem [66]. Approximately 20% of ICU pa-
Advantages tients in a general ICU have significant arrhythmias, mostly
Despite technical problems, direct arterial pressure measure- atrial fibrillation or ventricular tachycardia [67]. There is also
ment offers several advantages. Arterial lines actually measure a substantial incidence of arrhythmia following major surgery
the end-on pressure propagated by the arterial pulse. In con- [68]. Although no studies address whether monitoring for ar-
trast, indirect methods report the external pressure necessary rhythmias in a general ICU population alters outcomes, this
either to obstruct flow or to maintain a constant transmu- monitoring is generally accepted and considered standard care
ral vessel pressure. Arterial lines can also detect pressures at [66]. In postmyocardial infarction patients, on the other hand,
which Korotkoff sounds are either absent or inaccurate. Arte- the data is compelling. Arrhythmia monitoring was shown to
rial lines provide a continuous measurement, with heartbeat- improve the prognosis of patients admitted to the ICU for acute
to-heartbeat blood pressures. In situations in which frequent myocardial infarction (AMI) many years ago [69]. It has been a
blood drawing is necessary, indwelling arterial lines eliminate standard of care in the United States since that time. Although
the need for multiple percutaneous punctures. Finally, analy- ventricular tachycardia and fibrillation after myocardial infarc-
sis of the respiratory change in systolic or pulse pressure may tion have declined in frequency over the years, they still occur
provide important information on cardiac preload and fluid in about 7.5% of patients [70]. Monitoring enables the rapid
responsiveness. detection of these potentially lethal rhythms.

Conclusions Evolution of Arrhythmia Monitoring Systems


for Clinical Use
Indirect methods of measuring the blood pressure estimate the
arterial pressure by reporting the external pressure necessary to After ICUs implemented continuous ECG monitoring, practi-
either obstruct flow or maintain a constant transmural vessel tioners recognized some deficiencies with the systems. Initially,
size. Arterial lines measure the end-on pressure propagated by the responsibility for arrhythmia detection was assigned to spe-
the arterial pulse. Direct arterial pressure measurement offers cially trained coronary care nurses. Despite this, several studies
several advantages in many but not all patients. Although an documented that manual methods failed to identify arrhyth-
invasive line is required, the reported risk of complications is mias, including salvos of VT, in up to 80% of cases [71]. This
low [60]. Arterial lines provide a heartbeat-to-heartbeat mea- failure was probably due to an inadequate number of staff
surement, can detect pressures at which Korotkoff sounds are nurses to watch the monitors, inadequate staff education, and
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Chapter 26: Routine Monitoring of Critically Ill Patients 233

faulty monitors [72]. Subsequently, monitors equipped with lead ECG from four recording electrodes and a reference elec-
built-in rate alarms that sounded when a preset maximum or trode. Good correlation has been demonstrated between the
minimum rate was detected proved inadequate because some EASI system and traditional 12-lead ECG in detection of ST
runs of VT are too brief to exceed the rate limit for a given segment deviation in acute myocardial ischemia and also in
time interval [71,73]. Ultimately, computerized arrhythmia de- analyzing cardiac rhythm [80]. Other proposed enhancements
tection systems were incorporated into the monitors. The soft- to continuous ECG monitoring include signal-averaged ECG,
ware in these systems is capable of diagnosing arrhythmias QT dispersion, QT interval beat-to-beat variability, and heart
based on recognition of heart rate, variability, rhythm, inter- rate variability [81]. Although associated with subsequent ar-
vals, segment lengths, complex width, and morphology [74]. rhythmic events, these have not yet reached common clinical
These systems have been validated in coronary care and general use.
medical ICUs [71,75]. Computerized arrhythmia detection sys-
tems are well accepted by nursing personnel, who must work
most closely with them [76]. Technical Considerations
As with any other biomedical measurement, technical problems
Ischemia Monitoring can arise when monitoring cardiac rhythms. Standards have
been devised to guide manufacturers and purchasers of ECG-
Just as simple monitoring systems can miss episodes of VT monitoring systems [82].
and ventricular fibrillation, they can fail to detect significant The possibility of electrical shock exists whenever a patient
episodes of myocardial ischemia. This is either because the is directly connected to an electrically operated piece of equip-
episode is asymptomatic or because the patients ability to com- ment by a low-resistance path. Electrical shocks would most
municate is impaired by intubation or altered mental status. commonly occur with improper grounding of equipment when
ECG monitoring systems with automated ST segment analysis a device such as a pacemaker is in place. Necessary precautions
have been devised to attempt to deal with this problem. to avoid this potential catastrophe include (a) periodic checks
In most ST segment monitoring systems, the computer ini- to ensure that all equipment in contact with the patient is at
tially creates a template of the patients normal QRS complexes. the same ground potential as the power ground line; (b) insu-
It then recognizes the QRS complexes and the J points of sub- lating exposed lead connections; and (c) using appropriately
sequent beats and compares an isoelectric point just before the grounded plugs [83]. Each hospitals biomedical engineering
QRS with a portion of the ST segment 60 to 80 milliseconds department should have a documented preventive maintenance
after the J point [77]. It compares this relationship to that of the plan for all equipment in the unit.
same points in the QRS complex template. The system must de- The size of the ECG signal is important for accurate recog-
cide whether the QRS complex in question was generated and nition of cardiac rate and rhythm. Several factors may affect
conducted in standard fashion or whether the beats are aber- signal size. The amplitude can be affected by mismatching be-
rant, which negates the validity of comparison. Therefore, an tween skin-electrode and preamplifier impedance. The combi-
arrhythmia detection system must be included in all ischemia nation of high skin-electrode impedance, usually the result of
monitoring systems. Standard systems can monitor three leads poor contact between the skin and electrode, with low-input
simultaneously. These leads are usually chosen to represent the impedance of the preamplifier can decrease the size of the ECG
three major axes (anteroposterior, left-right, and craniocaudal]. signal. Good skin preparation, site selection, and conducting
The machine can either display these axes individually or sum gels can promote low skin-electrode impedance. A high pream-
up the ST segment deviations and display them in a graph over plifier input impedance or the use of buffer amplifiers can also
time [77]. improve impedance matching and thereby improve the signal
Automated ST segment analysis has gained widespread pop- obtained. Another factor that affects complex size is critical
ularity among cardiologists. Since 1989, the American Heart damping, the systems ability to respond to changes in the in-
Association has recommended that ischemia monitoring be in- put signal. An underdamped system responds to changes in in-
cluded in new monitoring systems developed for use in the put with displays that exaggerate the signal, called overshoot.
coronary care unit [78]. In patients admitted for suspected An overdamped system responds slowly to a given change and
acute coronary syndromes, ischemia is both frequently silent may underestimate actual amplitude. The ECG signal can also
and strongly associated with adverse events after discharge be affected by the presence of inherent, unwanted voltages at
[66]. Although noting that no randomized clinical trials doc- the point of input. These include the common mode signal, a
ument improved patient outcomes when automated ST seg- response to surrounding electromagnetic forces; the direct cur-
ment monitoring is used to detect ischemia, the American Heart rent skin potential produced by contact between the skin and
Association recommends ST segment monitoring for patients the electrode; and a potential caused by internal body resis-
with a number of primary cardiac issues (for example, acute tance. Finally, the ECG system must have a frequency response
coronary syndromes), based on expert opinion. The guidelines that is accurate for the signals being monitored. Modern, com-
make no statement regarding ST segment monitoring for ICU mercially available systems have incorporated features to deal
patients [66]. with each of these problems.

Newer Techniques Personnel


Because conventional three-lead monitoring detects only about The staffs ability to interpret the information received is cru-
one third of transient ischemic events in patients with unstable cial to effective ECG monitoring [78]. Primary interpretation
coronary syndromes [79], some authors have advocated the use may be by nurses or technicians under the supervision of a
of continuous 12-lead ECG systems in the care of acute coro- physician. All personnel responsible for interpreting ECG mon-
nary syndromes. However, continuous 12-lead ECG monitor- itoring should have formal training developed cooperatively
ing can be impractical given the large number of leads required, by the hospitals medical and nursing staffs. At a minimum,
patient discomfort, interference with medical procedures and this training should include basic ECG interpretation skills
proclivity to motion artifact. Some systems based on the dipole and arrhythmia recognition. Hospitals should also establish
hypothesis of vectorcardiography allow the derivation of a 12- and adhere to formal protocols for responding to and verifying
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234 Section II: Minimally Invasive Monitoring

alarms. Finally, a physician should be available in the hospi-


tal to assist with interpretation and make decisions regarding Respiratory Rate, Tidal Volume,
therapy. and Minute Ventilation
Clinical examination of the patient often fails to detect clin-
ically important changes in respiratory rate and tidal volume
Principles of Telemetry [86]. Physicians, nurses, and hospital staff frequently report in-
Intensive care patients frequently continue to require ECG accurate respiratory rates, possibly because they underestimate
monitoring after they are released from the ICU, and many the measurements importance [87]. In another study, ICU staff
postoperative critical care patients begin mobilization while in had a greater than 20% error more than one-third of the time
the ICU. At this point, increased mobility is important to allow when the recorded respiratory rate was compared with objec-
physical and occupational therapy as well as other rehabilita- tive tracings [88]. This is particularly surprising since the res-
tion services. Telemetry systems can facilitate this. piratory rate is an especially important predictor of outcome
Telemetry means measurement at a distance biomedical in many severity of illness scores such as the APACHE series
telemetry consists of measuring various vital signs, including [89]. In fact, respiratory rate has been called the neglected
heart rhythm, and transmitting them to a distant terminal [84]. vital sign [90]. Providers clinical assessment of tidal volume
Telemetry systems in the hospital consist of four major compo- and minute ventilation is similarly inaccurate [91]. Therefore,
nents [84]: (a) A signal transducer detects heart activity through objective monitoring must be used because clinical evaluation
skin electrodes and converts it into electrical signals; (b) a radio is inaccurate.
transmitter broadcasts the electrical signal; (c) a radio receiver
detects the transmission and converts it back into an electrical Impedance Monitors
signal; and (d) the signal converter and display unit present ICUs commonly use impedance monitors to measure respira-
the signal in its most familiar format. Continuous telemetry tory rates and approximate tidal volume. These devices typi-
requires an exclusive frequency so the signal can be transmit- cally use ECG leads and measure changes in impedance gener-
ted without interruption from other signals, which means the ated by the change in distance between leads as a result of the
hospital system must have multiple frequencies available to al- thoracoabdominal motions of breathing. Obtaining a quality
low simultaneous monitoring of several patients. The teleme- signal requires placing the leads at points of maximal change
try signal may be received in one location or simultaneously in thoracoabdominal contour or using sophisticated comput-
in multiple locations, depending on staffing practices. The sig- erized algorithms. Alarms can then be set for a high and low
nal transducer and display unit should also be equipped with rates or for a percentage drop in the signal that is thought to
an automatic arrhythmia detection and alarm system to allow correlate with a decrease in tidal volume.
rapid detection and treatment of arrhythmias. Notably, teleme- In clinical use, impedance monitors suffer confounding
try systems may be subject to interference by cellular phones problems. They have failed to detect obstructive apnea when
[85] or other radio equipment. it has occurred and falsely detected apnea when it has not
[92,93]. About one third of all apnea alarms from this tech-
nology are false-positives [94]. In situations with moving pa-
Summary tients, they are even less accurate for the quantification of res-
piratory rate [95]. Impedance monitors are poor detectors of
The American Heart Association recommends continuous ECG obstructive apnea because they may count persistent chest wall
monitoring for the detection of arrhythmias as a Class I in- motion as breaths when the apneic patient struggles to over-
tervention for all ICU patients [66]. Because ICU staff can come airway obstruction [92,93]. In general, respiratory rate
miss a large percentage of arrhythmias when they use moni- monitoring in the ICU therefore results in a very high fraction
tors without computerized arrhythmia detection systems, these of clinically irrelevant alarms: in one study, only 4% of respi-
computerized systems should be standard equipment in ICUs, ratory alarms were deemed clinically relevant [96]. Although
especially those which care for patients with AMI. It appears impedance monitors offer the advantage of being very inex-
that computerized monitoring devices can also detect a signifi- pensive when ECG is already in use, they lack accuracy when
cant number of arrhythmias not noted manually in noncardiac precise measurements of apnea, respiratory rate, or tidal vol-
patients. A large percentage of these lead to an alteration in pa- ume are required.
tient care. Automated ST segment analysis facilitates the early
detection of ischemic episodes. Telemetry provides close mon- Respiratory Inductive Plethysmography
itoring of recuperating patients while allowing them increased Respiratory inductive plethysmography (RIP) measures
mobility. changes in the cross-sectional area of the chest and abdomen
that occur with respiration and processes these signals into res-
piratory rate and tidal volume. This technology may be familiar
RESPIRATORY MONITORING to providers and patients because it is often used in polysomno-
grams. Typically, two elastic bands with embedded wire are
Critical care personnel should monitor several primary respi- placed above the xiphoid and around the abdomen. As the
ratory parameters, including respiratory rate, tidal volume or cross-sectional area of the bands changes with respiration, the
minute ventilation, and oxygenation in critically ill patients. self-inductance of the coils changes the frequency of attached
Routine monitoring of carbon dioxide levels would be desir- oscillators. These signals are generally calibrated to a known
able, but the technology for monitoring these parameters is not gas volume, or may be internally calibrated so that further
yet developed enough to consider mandatory continuous mon- measurements reflect a percentage change from baseline rather
itoring. In mechanically ventilated patients, many physiologic than an absolute volume. RIP can accurately measure respira-
functions can be monitored routinely and continuously by the tory rate and the percentage change in tidal volume, as well as
ventilator. This section does not discuss monitoring by the me- detect obstructive apnea [9799]. RIP has been used to follow
chanical ventilator (see Chapter 31) but examines devices that lung volumes in patients undergoing high-frequency oscillatory
might be routinely used to monitor the aforementioned param- ventilation [100]. These measurements are more accurate than
eters continuously and noninvasively. impedance measurements [93]. However, some studies have
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Chapter 26: Routine Monitoring of Critically Ill Patients 235

found problems with RIPs estimation of lung volumes. No- cians and nurses who use pulse oximeters do not understand
tably, RIP must be calibrated against a known gas volume in or- their underlying fundamental principles [110]. This section re-
der to provide tidal volume estimates. This calibration is not al- views the essential technology involved in pulse oximetry and
ways accurate and may result in errors of >10% in 5% to 10% practical problems that limit its use.
of patients even in highly controlled circumstances [97,101]. In
mechanically ventilated patients, RIP had significant measure- Theory. Oximeters distinguish between oxyhemoglobin and
ment drift (25 cm3 /min) and imprecise volume estimates. Only reduced hemoglobin on the basis of their different absorp-
about two thirds of tidal volume estimates were accurate to tion of light. Oxyhemoglobin absorbs much less red (660
within 10% of the reference value [102]. nm) and slightly more infrared (910 to 940 nm) light than
In addition to displaying respiratory rate and percentage nonoxygenated hemoglobin. Oxygen saturation thereby deter-
change in tidal volume, RIP can provide asynchronous and mines the ratio of red to infrared absorption. When red and
paradoxical breathing measurements and alarms, which are infrared light are directed from light-emitting diodes (LEDs) to
common during early weaning and may be helpful in predict- a photodetector across a pulsatile tissue bed, the absorption of
ing respiratory failure [103]. The noninvasive nature of the each wavelength by the tissue bed varies cyclically with pulse.
tidal volume measurement may be helpful in patients in whom During diastole, absorption is due to the nonvascular tissue
technical problems or leaks make it difficult to directly measure components (e.g., bone, muscle, and interstitium) and venous
expired volume (e.g., patients with bronchopleural fistulas]. In blood. During systole, absorption is determined by all of these
addition, RIP can display changes in functional residual capac- components and arterialized blood. The pulse amplitude ac-
ity, which permits health care providers to assess the effect of counts for only 1% to 5% of the total signal [111]. Thus,
changing positive end-expiratory pressure (PEEP). Providers the difference between absorption in systole and diastole is in
can determine the presence and estimation of the amount of theory due to the presence of arterialized blood. The change in
auto (intrinsic) PEEP by observing the effect of applied (ex- ratio of absorption between systole and diastole can then be
trinsic) PEEP on functional residual capacity [104], with the used to calculate an estimate of arterial oxygen saturation. Ab-
caveats noted earlier regarding possible inaccuracy of volume sorption is typically measured hundreds of times per second.
measurements. Signals usually are averaged over several seconds and then dis-
RIP systems are available with central station configura- played numerically. The algorithm used for each oximeter is
tions, which have been used in noninvasively monitored respi- determined by calibration on human volunteers. Most oxime-
ratory care units; these units have allowed ICU-level patients ters under ideal circumstances measure the saturation indicated
to be safely moved to a less-expensive level of care [105]. Com- by the pulse oximeter (SpO2 ) to within 2% of arterial oxygen
pared with impedance methods, RIP is more accurate and offers saturation [112].
a variety of other useful measurements but is less convenient Cooximeters perform measurements on whole blood ob-
and more expensive. tained from an artery or a vein. They frequently measure ab-
sorbance at multiple wavelengths and compute the percentage
Other Methods of oxyhemoglobin, deoxyhemoglobin, methemoglobin, and
carboxyhemoglobin (COHb) in total hemoglobin based on dif-
Although health care providers can also use pneumotachome- ferent absorption spectra. They are mostly free of the artifacts
ters, capnographs, and electromyography to accurately mea- that limit the accuracy of tissue oximeters and are regarded as
sure respiratory rate, these methods are not commonly used the gold standard by which other methods of assessing satura-
in the ICU. A pneumotachometer requires complete collection tion are measured.
of exhaled gas and, therefore, either intubation or use of a
tight-fitting face mask is not practical simply for monitoring. A Technology. Many manufacturers market pulse oximeters. Be-
second alternative, capnography, works exceedingly well as a cause of the variety of manufacturers, the numerous algorithms
respiratory rate monitor. Because it does not require intubation used, and the diverse patient populations studied, it is difficult
or a face mask, it can be a useful tool in many circumstances. to generalize the studies performed with one particular instru-
Capnography is discussed in more detail later. A third option, ment, with its specific version of software, in one defined group
surface electromyography of respiratory muscles can be used of patients, to critically ill patients in general. The reader should
to calculate respiratory rate accurately [106] but cannot detect always check with an oximeters manufacturer before general-
obstructive apnea or provide a measure of tidal volume. Elec- izing the following discussion to his or her oximeter and patient
tromyography works well in infants but presents difficulties in population.
adults, especially in obese adults and those with edema.
Recently, substantial research has focused on better ways Problems Encountered in Use. Because pulse oximeters are
to noninvasively monitor respiratory rate. All of these need ubiquitous, all ICU providers must understand their limita-
clinical validation in a critical care setting, but examples of tions. A meta-analysis of problems encountered in pulse oxime-
potentially emerging technologies include mechanical contact try trials found that severe hypoxemia, dyshemoglobinemia,
sensors placed in either patient beds or pillows, acoustical res- low perfusion states, skin pigmentation, and hyperbilirubine-
piratory monitoring, and photoplethysmography. mia may affect the accuracy of pulse oximeter readings [109].
Any process that affects or interferes with the absorption of
light between the LEDs and photodetector, alters the quality
Measurements of Gas Exchange of pulsatile flow, or changes the hemoglobin may distort the
oximeters calculations. Pulse oximeters should be able to ob-
tain valid readings in 98% of patients in an operating room
Pulse Oximetry or postanesthesia care unit [113]. Table 26.1 lists the problems
Clinical estimation of hypoxemia is exceptionally unreli- that must be considered in clinical use.
able [107,108]. Pulse oximeters measure the saturation of
hemoglobin in the tissue during the arterial and venous phases Calibration. Manufacturers use normal volunteers to derive
of pulsation and mathematically derive arterial saturation. pulse oximeter calibration algorithms. This creates three prob-
Meta-analysis of 74 oximeter studies suggests that these es- lems. First, manufacturers use different calibration algorithms,
timates are usually accurate within 5% of simultaneous gold which results in a difference in SpO2 of up to 2.7% between
standard measurements [109]. However, up to 97% of physi- different manufacturers oximeters used to measure the same
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236 Section II: Minimally Invasive Monitoring

TA B L E 2 6 . 1 Skin color. The effect of skin color on SpO2 was assessed


in a study of 655 patients [126]. Although patients with the
CONDITIONS ADVERSELY AFFECTING ACCURACY darkest skin had significantly less accurate SpO2 readings, the
OF OXIMETRY mean inaccuracy in SpO2 (compared with cooximetry) between
subjects with light skin and those with the darkest skin was
May result in poor signal detection only 0.5%, a clinically insignificant difference. Pulse oxime-
Probe malposition No pulse ters, however, encountered difficulties in obtaining readings in
Motion Vasoconstriction darker-skinned patients; 18% of patients with darker skin trig-
Hypothermia Hypotension gered warning lights or messages versus 1% of lighter skinned
Falsely lowers SpO2 Falsely raises SpO2 patients. A study of 284 patients with a newer generation
Nail polish Elevated carboxyhemoglobin oximeter also found that skin color did not affect measure-
Dark skin Elevated methemoglobin ment accuracy. Poor-quality readings were found more often in
Ambient light Ambient light darker skinned patients, although this was a rare event (<1%
Elevated serum lipids Hypothermia of all patients) [127]. Thus, dark skin may prevent a measure-
Methylene blue ment from being obtained, but when the oximeter reports an
Indigo carmine error-free value, the value is generally accurate enough for clin-
Indocyanine green ical use [128].

SpO2 , saturation indicated by the pulse oximeter. Ambient light. Ambient light that affects absorption in the
660- or 910-nm wavelengths, or both, may affect calculations
of saturation and pulse. Xenon arc surgical lights [129], fluores-
cent lights [130], and fiberoptic light sources [131] have caused
falsely elevated saturation but typically obvious dramatic ele-
patient [114]. Second, manufacturers define SpO2 differently vations in reported pulse. An infrared heating lamp [132] has
for calibration purposes. Calibration may or may not account produced falsely low saturations and a falsely low pulse, and
for the interference of small amounts of dyshemoglobinemia a standard 15-W fluorescent bulb resulted in falsely low satu-
(e.g., methemoglobin or COHb). For example, if an oximeter ration without a change in heart rate [133]. Interference from
is calibrated on the basis of a study of nonsmokers with a 2% surrounding lights should be suspected by the presence of pulse
COHb level, the measured SpO2 percentage would differ de- values discordant from the palpable pulse or ECG, or changes
pending on whether the value used to calibrate SpO2 included in the pulse-saturation display when the probe is transiently
or excluded the 2% COHb [114]. Third, it is difficult, for eth- shielded from ambient light with an opaque object. Most man-
ical reasons, for manufacturers to obtain an adequate num- ufacturers have now modified their probes to minimize this
ber of validated readings in people with an SpO2 of less than problem. Studies report that ambient lighting has little or no ef-
70% to develop accurate calibration algorithms in this satura- fect on newer generation oximeters [134], although this varies
tion range. Most oximeters give less precise readings in this among manufacturers [135].
saturation range [115]. Unless better calibration algorithms
become available, oximeters should be considered unreliable Hyperbilirubinemia. Bilirubins absorbance peak is maximal
when SpO2 is less than 70%, although this may have little clin- in the 450-nm range but has tails extending in either direc-
ical impact since emergent intervention is usually required for tion [136]. Bilirubin, therefore, does not typically affect pulse
all SpO2 readings <70%. oximeters that use the standard two-diode system [136,137].
However, it may greatly interfere with the measurement of sat-
Measurement sites. Careful sensor positioning is crucial to ob- uration by cooximeters. Cooximeters typically use four to six
taining accurate results from a pulse oximeter [116]. Practition- wavelengths of light and measure absolute absorbance to quan-
ers can obtain accurate measurements from fingers, forehead, tify the percentage of all major hemoglobin variants. Serum
and earlobes. The response time from a change in the partial bilirubin values as high as 44 mg per dL had no effect on the
pressure of arterial oxygen (PaO2 ) to a change in displayed accuracy of pulse oximeters but led to falsely low levels of oxy-
SpO2 is delayed in finger and toe probes compared with ear, hemoglobin measured by cooximetry [136].
cheek, or glossal probes [117,118]. Forehead edema, wetness,
and head motion may result in inaccurate forehead SpO2 values Dyshemoglobinemias. Conventional (two-diode) pulse oxime-
[119]. Motion and perfusion artifacts are the greatest problems ters cannot detect the presence of methemoglobin, COHb, or
with finger or toe measurements. The earlobe is believed to be fetal hemoglobin. Fetal hemoglobin may confound readings
the site least affected by vasoconstriction artifact [120], but in neonates but is rarely a problem in adults. On the other
paradoxically the finger may give a better signal in times of hand, acquired methemoglobinemiaalthough uncommon
hypoperfusion [109]. is seen in routine practice, largely due to the use of methe-
moglobinemia-inducing drugs such as topical anesthetics
Fingernails. Long fingernails may prevent correct positioning [138]. Because methemoglobin absorbs more light at 660 nm
of the finger pulp over the LEDs used in inflexible probes and than at 990 nm, it affects pulse oximetry readings [139]. More-
therefore produce inaccurate SpO2 readings without affecting over, higher levels of methemoglobin tend to bias the read-
the pulse rate [121]. Synthetic nails have produced erroneous ing toward 85% to 90% [140]. COHb is typically read by a
results [112]. Adhesive tape, even when placed over both sides two-diode oximeter as 90% oxyhemoglobin and 10% reduced
of a finger, did not affect measured SpO2 [122]. Since pulse hemoglobin [141], resulting in false elevations of SpO2 . A gap
oximetry depends fundamentally on color, nail polish may between pulse oximetry and pO2 or cooximetrically measured
falsely lower SpO2 . In a 1988 study, blue, green, and black oxygen saturation may suggest elevated COHb levels, partic-
polish showed greater decreases than red or purple [123]. How- ularly in patients with smoke inhalation or potential carbon
ever, a 2002 study with a newer-generation oximeter did not monoxide poisoning [142]. Because COHb may routinely be
find this effect [124]. In addition, placing the probe sideways 10% in smokers, pulse oximetry may fail to detect significant
across the fingernail bed appeared to ameliorate any effect of desaturation in this group of patients. Oxygen saturation in
fingernail polish in one study [125]. smokers, when measured by cooximetry, was on average 5%
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Chapter 26: Routine Monitoring of Critically Ill Patients 237

lower than pulse oximetric values [143]. Hemolytic anemia by the oximeter may no longer reflect the presence of just arte-
may also elevate COHb up to 2.6% [144]. Because other eti- rial blood. In patients with severe tricuspid regurgitation, the
ologies of COHb are rare in the hospital and the half-life of measured saturation may be falsely low, especially with ear
COHb is short, this problem is unusual in the critical care probes [160].
setting except in newly admitted patients, patients with active
hemolysis, or those on COHb-inducing drugs such as sodium Indications. The Society of Critical Care Medicine considers
nitroprusside [145]. More recently, some pulse oximeters that pulse oximetry (or transcutaneous oxygen measurement) es-
use multi-wavelength technology have been able to successfully sential monitoring for all ICU patients receiving supplemental
report methemoglobin and COHb levels [146]. oxygen [161]. Unsuspected hypoxemia is common in critically
ill patients. Sixteen percent of patients not receiving supple-
Anemia. Few clear data are available on the effect of anemia on mental oxygen in the recovery room have saturations of less
pulse oximetry. In dogs, there was no significant degradation in than 90% [162]. In 35% of patients, saturations of less than
accuracy until the hematocrit was less than 10% [147]. In one 90% develop during transfer out of the operating room [163].
study of humans who had hemorrhagic anemia, there appeared Because of the high frequency of hypoxemia in critically ill pa-
to be little effect on pulse oximetry accuracy [148]. tients, the frequent need to adjust oxygen flow, and the unrelia-
bility of visual inspection to detect mild desaturation, oximeters
Lipids. Patients with elevated chylomicrons and those receiv- should be used in most critically ill patients for routine, con-
ing lipid infusions may have falsely low SpO2 because of in- tinuous monitoring. In one study that randomized more than
terference in absorption by the lipid [149]. This also affects 20,000 operative and perioperative patients to continuous or
cooximetry and may lead to spurious methemoglobin readings no oximetric monitoring, the authors concluded that oxime-
[150]. try permitted detection of more hypoxemic events, prompted
increases in the fraction of oxygen in inspired air, and signifi-
Hypothermia. Good-quality signals may be unobtainable in cantly decreased the incidence of myocardial ischemia but did
10% of hypothermic patients [151]. The decrease in signal not significantly decrease mortality or complication rates [164].
quality probably results from hypothermia-induced vasocon- Oximeters have been used in the ICU for reasons other than
striction. When good-quality signals could be obtained, SpO2 continuous monitoring. For example, oximeters may be help-
differed from cooximetry-measured saturation by only 0.6% ful during difficult intubations. Once desaturation occurs, at-
[151] in one series. tempts to intubate should be postponed until manual ventila-
tion restores saturation. Note, however, that oximetry is not
Intravascular dyes. Methylene blue, used to treat methe- helpful in promptly detecting inadvertent esophageal intuba-
moglobinemia, has a maximal absorption at 670 nm and there- tion because desaturation may lag significantly behind apnea
fore falsely lowers measured SpO2 [152]. Indocyanine green in preoxygenated patients [165]. Oximeters can be useful in de-
and indigo carmine also lower SpO2 , but the changes are mi- tecting systolic blood pressure (see arterial pressure monitoring
nor and brief [153]. Fluorescein has no effect on SpO2 [153]. earlier), and have been used in other clinical applications with
Because of the rapid vascular redistribution of injected dyes, varying degrees of success. Notably, a normal SpO2 reading
the effect on oximetry readings typically lasts only 5 to 10 min- should not be used to exclude pulmonary embolism [166].
utes [154]. Patent V dye, which is used to visualize lymphatics
in sentinel node mapping, confounds pulse oximetry, an effect Capnography
which may persist for more than 90 minutes [155]. Capnography involves the measurement and display of expired
PCO2 concentrations. This section reviews the technology, the
Motion artifact. Shivering and other motions that change the sources of difference between end-tidal PCO2 (EtCO2 ) and
distance from diode to receiver may result in artifact. Oxime- PaCO2 , and the indications for capnography in the ICU.
ters account for motion by different algorithms. Some oxime-
ters display a warning sign, others stop reporting data, and Technology. Expired PCO2 concentration is usually deter-
others display erroneous values. The display of a plethysmo- mined by infrared absorbance or mass spectrometry. The in-
graphic waveform rather than a signal strength bar helps to frared technique relies on the fact that carbon dioxide has a
indicate to providers that artifact has distorted the pulse signal characteristic absorbance of infrared light, with maximal ab-
and lowered the quality of the SpO2 reading. Newer genera- sorbance near a wavelength of 4.28 mm. A heated wire with
tion oximeters appear to have significantly less susceptibility to optical filters is used to generate an infrared light of appropri-
motion artifact than earlier models [156]. ate wavelength. When carbon dioxide passes between a focused
beam of light and a semiconductor photodetector, an electronic
Hypoperfusion. During a blood pressure cuff inflation model signal can be generated that, when calibrated, accurately re-
of hypoperfusion, most oximeters remained within 2% of con- flects the PCO2 of the tested gas.
trol readings [157]. Increasing systemic vascular resistance and A mass spectrometer bombards gas with an electron stream.
decreasing cardiac output can also make it harder to obtain a The ion fragments that are generated can be deflected by a
good-quality signal. In one series, the lowest cardiac index and magnetic field to detector plates located in precise positions to
highest systemic vascular resistance at which a signal could be detect ions that are characteristic of the molecule being eval-
detected were 2.4 L per minute per m2 and 2,930 dynes second uated. The current generated at the detector can be calibrated
per cm5 per m2 , respectively [158]. Warming the finger [159] or to be proportional to the partial pressure of the molecule being
applying a vasodilating cream [158] tended to extend the range evaluated.
of signal detection in individual patients. The oximeters ability The two techniques have different strengths. Mass spec-
to display a waveform and detect perfusion degradation of the trometers can detect the partial pressures of several gases simul-
signal was crucial in determining when the readings obtained taneously and can monitor several patients at once. Infrared
were valid [157]. techniques measure only PCO2 and are usually used on only
one patient at a time. The calibration and analysis time re-
Pulsatile venous flow. In physiologic states in which venous quired for mass spectrometry is significantly longer than with
and capillary flows become pulsatile, the systolic pulse detected infrared techniques. Infrared systems respond to changes in
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238 Section II: Minimally Invasive Monitoring

approximately 100 milliseconds, whereas mass spectrometers


take 45 seconds to 5 minutes to respond [167]. Although costs
vary widely, mass spectrometers are in general far more ex-
pensive and are most frequently purchased to be the central
component of a carbon dioxide monitoring system. In the op-
erating room, mass spectrometry has the advantage of being
able to measure the partial pressure of anesthetic gases, and
the need for a technical specialist to oversee its operation can A
be more easily justified. For these reasons, mass spectrometry
has achieved much more popularity in the operating room than
in the ICU.
Gases can be sampled by mainstream or sidestream tech-
niques. Mainstream sampling involves placing the capnometer
directly in line in the patients respiratory circuit. All air leaving
the patient passes through the capnometer. The sidestream sam-
pling techniques pump 100 to 300 mL expired air per minute
B
through thin tubing to an adjacent analyzing chamber.
The mainstream method can be used only on patients who
are intubated or wearing a tight-fitting face or nose mask.
Mainstream sampling offers the advantage of almost instanta-
neous analysis of sampled air, but it increases the patients dead
space and adds weight to the endotracheal tube. Sidestream
sampling removes air from the expiratory circuit, altering mea-
surement of tidal volume. Slower aspirating flow rates and C
longer tubing lengths significantly worsen the ability to detect
a rapid rise in carbon dioxide and cause delay between phys-
iologic changes in the patient and the display of changes on
the monitor [168]. When the delay exceeds the respiratory cycle
time, the generated data are inaccurate [168]. Located near the
mouth or nose, sidestream sampling lines are also prone to clog- D
ging with secretions, saliva, or water condensation. Sidestream
sampling can be used in nonintubated patients to detect FIGURE 26.1. Normal and abnormal capnograms. In the normal
cyclic changes in carbon dioxide concentrations. Because of capnogram (A), on the right of the trace, the paper speed has been
these issues, accurate sidestream sampling requires short sam- increased. The EF segment is inspiration. The FG segment reflects
pling tubes and attention to the possibility of clogged sample the start of expiration with exhalation of dead space gas. The GH
lines. segment is the alveolar plateau. End-tidal values are taken at point
H. HI is the beginning of inspiration. In the abnormal capnograms, the
Differences Between End-Tidal and Arterial Carbon Dioxide. alveolar plateau is distorted and the end-tidal point cannot be clearly
determined because of cardiac oscillations (B), erratic breathing (C),
The PCO2 in exhaled air measured at the mouth changes in and obstructive airway disease (D). ECG, electrocardiogram. (Mod-
a characteristic pattern in normal people that reflects the un- ified from Stock MC: Noninvasive carbon dioxide monitoring. Crit
derlying physiologic changes in the lung (Fig. 26.1). During Care Clin 4:511, 1988.)
inspiration, the PCO2 is negligible, but it rises abruptly with
expiration. The rapid rise reflects mixing and the washout of
dead-space air with air from perfused alveoli, which contain
higher levels of CO2 . A plateau concentration is reached af- can detect situations in which algorithms are prone to produce
ter dead-space air has been exhaled. The plateau level is de- errors [167].
termined by the mean alveolar PCO2 , which is in equilibra-
tion with pulmonary artery PCO2 . The end-alveolar plateau Indications. In the ICU, capnography is most useful for (1)
level of PCO2 measured during the last 20% of exhalation detection of extubation, (2) determining the presence or ab-
is the EtCO2 . In normal people at rest, the difference be- sence of respiration, and (3) detecting return of spontaneous
tween EtCO2 and PaCO2 is 1.5 mm Hg. A difference exists circulation after cardiac arrest. Such determinations do not re-
because of the presence of dead space and a normal physio- quire that EtCO2 be measured accurately, only that changes be
logic shunt. Changes in dead space or pulmonary perfusion detected reliably. Alarms for apnea and tachypnea can be set
alters ventilationperfusion ratio and changes the relationship and relied on, although capnography cannot discriminate be-
between end-tidal and arterial PCO2 values. As dead space in- tween obstructive and central apnea. Capnography is a useful
creases, the EtCO2 represents more the (lower) PCO2 of non- adjunct for detecting unintentional extubation, malposition of
perfused alveoli, thereby diverging from the PaCO2 value. As the endotracheal tube, or absence of perfusion. Cyclic varia-
perfusion decreases, fewer alveoli are perfused, creating a sim- tion of EtCO2 is absent in esophageal intubation or disconnec-
ilar effect. tion from the ventilator [169]. Although pharyngeal intubation
In most equipment, the EtCO2 level is determined by a with adequate ventilation may produce a normal capnogram.
computerized algorithm. Because algorithms are imperfect, a Capnography can demonstrate the return of circulation after
waveform display is considered essential for accurate interpre- cardiopulmonary arrest or bypass. In full cardiac arrest, EtCO2
tation of derived values [168]. In slowly breathing patients, car- is low because of lack of perfusion; a rapid rise in EtCO2 indi-
diac pulsations may cause the intermittent exhalation of small cates return of circulation and successful delivery of CO2 to the
amounts of air at the end of the lungs expiratory effort. This alveoli [170]. Capnography or capnometry is also frequently
results in oscillations that may obscure the plateau phase. An used to help detect esophageal intubation [171].
irregular respiratory pattern or large increases in dead space EtCO2 measurements are unreliable indicators of PaCO2 in
can also distort the plateau phase. Visual inspection of traces critically ill patients. Since these patients undergo rapid changes
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Chapter 26: Routine Monitoring of Critically Ill Patients 239

in dead space fraction and pulmonary perfusion, the relation- scutaneous values of oxygen and carbon dioxide are typically
ship of EtCO2 to arterial PaCO2 may change rapidly and unpre- 10 mm Hg lower [177] and 5 to 23 mm Hg higher [178] than
dictably. In one study of anesthetized, stable, generally healthy arterial values, respectively.
adults, PaCO2 could not be reliably determined from end-tidal However, local pO2 and pCO2 therefore depend not only
values [172]. In patients undergoing weaning from mechanical on global gas exchange, cardiac output, and oxygen content,
ventilation, EtCO2 was also shown to have no predictable re- but also on regional blood flow and oxygen delivery to the
lationship to PaCO2 [173]. Although end-tidal and arterial val- site of measurement. Under normal circumstances, oxygen de-
ues correlated well (r = 0.78) and rarely differed by more than livery far exceeds consumption. In critical illness, however, re-
4 mm Hg, changes in EtCO2 correlated poorly with changes gional hypoperfusion or inadequate regional delivery of oxygen
in arterial PCO2 (r 2 = 0.58]. Because of changes in dead space may occur for any number of reasons: hypotension, regional
and perfusion, arterial and end-tidal measurements at times vasoconstriction, low cardiac output states, anemia, vascular
moved unpredictably in opposite directions. Although theoret- occlusion, etc. If there is no flow to the region, there can be
ically attractive, the use of end-tidal carbon dioxide measure- no delivery of oxygen and no elimination of carbon dioxide
ments to evaluate changes in ventilation-perfusion mismatch by the vasculaturethus creating lower local pO2 and higher
in response to ventilator changes has failed to yield consistent local pCO2 than in the arterial circulation. When tissue is hy-
clinical benefits [174]. poperfused, local metabolism then further alters local pO2 and
Capnography has been helpful in the operating room in pCO2 . As cellular processes use available oxygen for the pro-
detecting air and pulmonary embolism as well as malignant duction of adenosine triphosphate (ATP), local pO2 falls. When
hyperthermia [167]. In these situations, the capnograph does these cells use ATP faster than they replenish it, they liberate
not provide a diagnosis; it records a change that, if limits are hydrogen ions (H+ ) and reduce local pH. (Alternatively, cells
exceeded, signals an alarm. The responsibility for accurately may produce lactic acid through the anaerobic metabolic path-
interpreting the subtleties of changes in the capnogram remains way.) These addition hydrogen ions are then buffered by tis-
the task of an experienced physician. sue bicarbonate, generating CO2 : H+ + HCO 3 H2 O3
H2 O + CO2. This increases local pCO2 above corresponding
Conclusions. Capnography is of limited use in the critically ill global/arterial values [179]. For these reasons, local pO2 and
patient. In any patient with changing cardiac output, fluctu- pCO2 therefore vary not only with global gas exchange, but
ating respiratory function, or chronic lung disease, it should also with local tissue perfusion.
not be used to replace PaCO2 monitoring. It has been used
to assess correct endotracheal tube placement (or inadvertent
extubation) and offers rapid information about the return of Gastric Tonometry
spontaneous circulation after cardiac arrest. It does, however,
monitor respiratory rate accurately and may be useful in some Gastric tonometry, probably the most commonly used of the
circumstances for that function. Capnography may be better three perfusion monitoring techniques discussed in this sec-
suited to the operating room, where its value is increased be- tion, assesses regional splanchnic perfusion based on the stom-
cause of its ability to help detect endotracheal tube malposition, achs mucosal pCO2 . The splanchnic circulation has several
air embolism, pulmonary embolism, and malignant hyperther- properties which make this region particularly useful to as-
mia, and where there is a highly skilled anesthesiologist imme- sess in critically ill patients. Early in the development of shock
diately available to interpret subtle changes in the capnogram. states, the splanchnic circulation vasoconstricts, shunting car-
diac output toward other core organs. Although this helps to
prevent circulatory collapse, it may also result in intestinal mu-
NONINVASIVE TISSUE cosal ischemiaincreasing the risk of gastric stress ulceration,
PERFUSION MONITORING mesenteric ischemia, and translocation of gut bacteria into the
systemic circulation [180]. The gut is particularly sensitive to
Bedside providers usually monitor tissue perfusion based on hypoperfusion and so may provide earlier warning of occult hy-
clinical signs such as skin temperature and capillary refill time. poperfusion than other vascular bedsleading some to liken
However, several noninvasive technologies provide quantita- it to a coal miners canary [181]. Gastric tonometry measures
tive data about overall or regional tissue perfusion. Unlike most gastric luminal pCO2 and estimates gastric intramucosal pCO2
of the other monitoring technologies described in this chapter, and pH (pHi).
clinical adoption of these techniques has been relatively lim-
ited and heterogeneous [175]. This section reviews three such Technical Considerations
technologies that measure local pCO2 or pO2 : gastric tonom- Development. Early measurements of visceral mucosal pH re-
etry, sublingual capnometry, and transcutaneous oxygen and quired operative implantation of monitors and focused on the
carbon dioxide monitoring. Measurements from each of these gallbladder, urinary bladder, and small bowel [182,183]. De-
techniques correlate meaningful clinical outcomes such as pa- velopment of silastic tubing [184]which is exceptionally per-
tient survival. meable to O2 and CO2 and confirmation that gases in tissue
equilibrate rapidly with fluid in the lumen of a hollow vis-
cus [185] allowed development of the modern gastrointestinal
Physiology: Why Regional pO2 and pCO2 tonometer.
Reflects Tissue Perfusion and Not Just
Global Gas Exchange Technique. The upper gastrointestinal catheter is inserted with
standard technique for nasogastric tube placement, and place-
At first glance, it would appear that measurement of pO2 or ment is confirmed radiographically. The stopcock is flushed
pCO2 in the skin, stomach, or tongue would reflect global gas with fluid to eliminate any trapped air, the balloon is filled to
exchange and might be used for noninvasive blood gas estima- the manufacturers specifications with fluid, and the tonome-
tion. In some cases, this is true. In healthy adults, for example, ter lumen is closed to the outside environment. The fluid is
transcutaneously measured pO2 and CO2 (PtcO2 and PtcCO2 ) allowed to equilibrate with the fluid in the lumen of the organ
accurately reflect PaO2 and PaCO2 [176]. The measured tran- being monitored, a process believed to require approximately
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240 Section II: Minimally Invasive Monitoring

90 minutes, although formulas are available to correct the val- quent randomized, controlled trial of 210 general ICU patients,
ues obtained with 30 to 90 minutes of equilibration [186]. reported in 2000, found no difference between intervention and
After adequate time for equilibration, the dead space (usually control arms [204]. In patients with a normal initial pHi, there
1.0 mL) is aspirated and discarded, and the fluid in the balloon was a nonsignificant trend toward increased 30-day mortality
is completely aspirated under anaerobic conditions. An ABG in the group treated based on pHi. One patient in the interven-
sample is taken simultaneously, and both samples are sent for tion group was excluded from analysis due to a conversion to
analysis. The pCO2 of the tonometer sample is measured di- comfort-measures-only status 5 hours after enrollment. A 2005
rectly. Providers can then calculate an arterial/mucosal pCO2 study randomized 151 trauma patients to pHi-driven therapy,
gap or, using the HCO3 of arterial blood and the modified splanchnic ischemia/reperfusion-based protocol, or usual care.
HendersonHasselbalch equation, pHi [187,188]. The authors found no significant differences in mortality, or-
An air-based tonometer has also gained popularity. This de- gan dysfunction, ventilator days, or length of stay. Analysis was
vice operates on the same principles as the saline-based tonome- intention-to-treat [205]. Other, smaller randomized trials have
ter, but automatically aspirates small amounts of air from a generally found no effect [206].
semipermeable balloon. This is substantially more convenient
than the saline-based device, and allows semicontinuous mea- Alternative Regional pCO2 Measurement: Sublingual Cap-
surement of gastric mucosal pCO2 . Results are generally similar nometry. Sublingual capnometry operates on the same fun-
to saline-based tonometry [189]. damental principles as gastric tonometry. A sensor is placed
under the tongue and CO2 diffuses across a semipermeable
Technical Limitations. Several issues may confound the clini- membrane into a dye, which fluoresces differently based on
cal use of gastric tonometry. Two of these apply only to saline- CO2 concentration. A fiberoptic cable transmits light of the
based tonometry. The fluid in the tonometer balloon requires appropriate wavelength and detects the resulting fluorescence,
90 minutes for full equilibration with the fluid in the stomach. which is proportional to CO2 concentration in the sensor [175].
In a rapidly changing patient, this time window may not be ap- Results from this technique correlate with gastric tonome-
propriately timely. In addition, manufacturers calibrate blood try [207] and patient outcome [208]. No randomized inter-
gas analyzers to measure pCO2 in blood, not saline. pCO2 mea- vention trials based on sublingual capnometry have yet been
surements in tonometer saline, therefore, may vary based on published. Although sublingual capnometry was entering non-
the blood gas analyzer used [190]. Other limitations apply to research clinical use, the manufacturer recalled the commer-
the general principle of measure gastric luminal pCO2 to es- cially available sublingual capnometry device in 2004 after an
timate mucosal perfusion. Tonometrically derived gastric pHi outbreak of Burkholderia cepacia related to contaminated sub-
can be affected by the acid-secretory status of the stomach. lingual probes [209].
In one study, mean gastric pHi was 7.30 in untreated normal
volunteers but 7.39 in a similar group treated with ranitidine Summary. Although gastric tonometry predicts many impor-
[191]. This was because the pCO2 in the gastric fluid of the tant clinical outcomes, high-quality data does not support
treated patients was 42 4 mm Hg, compared with 52 gastric-tonometrybased resuscitation. The Surviving Sepsis
14 mm Hg in the untreated group. The difference in carbon Campaigns 2004 guidelines for hemodynamic management
dioxide content of the fluid is thought to be due to production of septic shockrepresenting eleven international professional
of carbon dioxide by the conversion of secreted H+ and HCO3 societiesconcludes that these results make gastric tonometry
into water and carbon dioxide. Enteral feeding may also affect of interest largely as a research tool rather than as a useful
pHi reading. Tube feedings may lead to increased production clinical monitor for routine use [194]. Researchers are ac-
of carbon dioxide through the interaction of secreted hydro- tively investigating the use of sublingual capnometry, a similar
gen ions and HCO3 . Some suggest temporarily discontinuing technology, as a potential resuscitation endpoint.
tube feeds before doing pHi measurements [192], although the
pCO2 affect appears to diminish after 24 hours of continuous
feeding [193]. Finally, pHi is a calculated variable which uses Transcutaneous Oxygen and Carbon
the systemic arterial bicarbonate value; this probably does not
reflect regional perfusion [188]. The present consensus favors
Dioxide Measurement in Adults
the use of arterial-gastric pCO2 gap rather than pHi [189,194].
Transcutaneous measurements of the partial pressures of oxy-
gen (PtcO2 ) and carbon dioxide (PtcCO2 ) are frequently
Clinical Usefulness and Limitations. pHi correlates well with used for neonatal blood gas monitoring but have not gained
a number of clinically important endpoints. Changes in pHi widespread clinical acceptance in adult ICUs [175]. In adults,
during weaning from mechanical ventilation predict weaning similar to gastric tonometry, PtcO2 and PtcCO2 reflect local
failure [195]. Intraoperative and postoperative cardiac surgery tissue oxygen and carbon dioxide levels and therefore blur the
patients have been particularly well studied, and in that group boundary between assessment of global gas exchange and re-
gastric pHi appears to predict complications well [196,197]. gional tissue perfusion monitoring. More recently, measure-
Most importantly, pHi predicts mortality in septic [198], ments of transcutaneous hemoglobin oxygen saturation (StO2 )
acutely injured [199], and general ICU patients [200]. have entered the research and clinical realms.
For a diagnostic tool to be therapeutically useful, however, This section refers only to transcutaneous monitoring in
we must be able to act on its results in a way that improves adults.
patient outcome [201]. Therapeutic protocols based on gastric
tonometry have produced conflicting results. A randomized,
controlled trial of 260 ICU patients, reported in 1992, found
Technique
that gastric pHi-based therapy had no effect on mortality of Oxygen and carbon dioxide diffuse out of the capillaries, into
patients with a low admission pHi but was associated with re- the interstitium, and through the skin. The skin usually resists
duced mortality in patients with a normal admission pHi [202]. O2 and CO2 diffusion, but heating the skin promotes diffu-
However, interpretation of this finding is severely limited be- sion by changing the structure of the stratum corneum, shifting
cause the authors did not analyze the results in an intention-to- the oxygen dissociation curve, and promoting arterialization of
treat fashion, thus abandoning many of the benefits of random- dermal capillaries [175]. Transcutaneous systems take advan-
ization [203], and 21 patients were withdrawn from the study tage of these properties to measure partial pressures of oxygen
due to protocol noncompliance by treating physicians. A subse- (PtcO2 ) and carbon dioxide (PtcCO2 ). Typically, a unit less
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Chapter 26: Routine Monitoring of Critically Ill Patients 241

than 1 inch in diameter is attached with an airtight seal to the sion and metabolism may cause PtcO2 values to fall to zero
skin with an adhesive. An electrode heats the skin to improve and PtcCO2 values to climb to more than 30 mm Hg above
gas exchange; a temperature sensor measures skin temperature arterial values [212]. During cardiac decompensation and ar-
at the skin surface and adjusts the heater to provide a con- rest, PtcO2 correlates best with cardiac output [215]. In hem-
stant temperaturetypically about 44 C. Oxygen and carbon orrhagic shock, the ratio of PtCO2 to PaO2 decreases, even
dioxide diffuse out of the capillaries into the interstitium and though PaO2 may remain normal [216]. Because the measure-
through the skin to measuring electrodes. ments are very sensitive to changes in flow, they can be useful
in predicting or warning of imminent change before a blood
Technical Limitations pressure response is seen. In a small series of high-risk perioper-
ative patients, declines in the PtCO2 /PaO2 ratio predicted sub-
Because units use electrodes for partial pressure measurement,
sequent hemodynamic collapse [217]. Transcutaneous PtcO2
problems with calibration and electrode drift during prolonged
also correlates with mortality. In emergency department pa-
monitoring can clearly alter measurements. Drift may alter
tients with severe sepsis or septic shock, PtcO2 was lower in
readings by up to 12% over a 2-hour period [210]. Because of
nonsurvivors than survivors [218]. In trauma patients, PtcO2
the heating requirement, probe sites must be changed at least
values were significantly higher in survivors than nonsurvivors
every 4 hours to prevent burns [211]. Units must be recalibrated
( p < 0.001) with an area under the receiver operating char-
whenever the probe temperature is changed and every 4 to
acteristics curve of 0.74 for predicting in-hospital mortality
6 hours to prevent artifact from electrode drift. Many units take
[219].
15 to 60 minutes to warm the skin and establish stable readings.
Probes must be firmly attached to the skin, or leaks from the
surrounding atmosphere lower PtcCO2 and alter PtcO2 values.
Ongoing Development
Adhesion is a problem in diaphoretic patients. More recent work has focused on the use of near-infrared
Thick or edematous skin provides a diffusion barrier that spectroscopy to measure tissue hemoglobin oxygen satura-
amplifies differences between arterial and transcutaneous pO2 tion. This technique, rather than quantifying partial pres-
and pCO2 . The longer the distance the gases must diffuse to sures of oxygen, instead measures the percent of microvascular
be measured, the more important are the effects of temper- hemoglobin saturated with oxygen. It has shown clinical cor-
ature, perfusion, and local metabolism. This appears to be relations with invasive hemodynamic measures in sepsis [220]
the fundamental reason why transcutaneous measurements are and severity of shock in trauma [221]. Further research is re-
usually more closely related to arterial values in neonates than quired to define the role of StO2 as a potential resuscitation
in adults. Edema, burns, abrasions, or scleroderma would all endpoint.
be expected to alter transcutaneous values.
Summary
Clinical Usefulness and Limitations
Transcutaneous monitors have little role in the ICU as simple
Because PtcO2 and PtcCO2 reflect local pO2 and pCO2 , they tools to replace other means of measuring arterial gas. They
change in response both to regional perfusion/oxygen deliv- predictably reflect arterial pO2 and pCO2 values only in hemo-
ery and to global derangements. In stable, healthy adults with- dynamically stable patients, who are least likely to demand in-
out hemodynamic or respiratory instability, PtcO2 and PtcCO2 tensive care or to benefit from ICU monitoring. As monitors of
accurately reflect PaO2 and PaCO2 [176,210]. The measured trends in PCO2 and PO2 , they can be regarded as effective only
transcutaneous values of oxygen and carbon dioxide are typi- in the sense that they typically do not produce false-negative
cally 10 mm Hg lower [177] and 5 to 23 mm Hg higher [212] alarmsthat is, if the arterial values change, the transcuta-
than arterial values, respectively. In stable patients, it may be neous values reflect the change. So many other factors, such as
reasonable to use transcutaneously measured values as surro- changes in tissue edema and perfusion, may result in alterations
gates for arterial pO2 and pCO2 . However, systemic hypoper- in transcutaneous trends that the supervising staff can initially
fusion due to low cardiac output, regional hypoperfusion due determine only that something has changed. An accurate inter-
to sepsis or shock, and local hypoperfusion due to cutaneous pretation of the clinical event usually requires reassessment of
vasoconstriction caused by medication or cold produces dis- either cardiac status or arterial gases.
crepancies. In these cases, transcutaneous measurements cease Therefore, transcutaneous monitors are inadequate cardiac
to reflect arterial values and better track oxygen delivery and monitors and inadequate pulmonary monitors but are good
tissue metabolism [213]. For these reasons, many authors have cardiopulmonary monitors. When perfusion is stable, values
argued against relying on PtcO2 and PtcCO2 to estimate arte- reflect gas exchange. When gas exchange is stable, values
rial pO2 and pCO2 in critically ill adults [213,214]. reflect perfusion. When both are unstable, the results can-
Several studies have demonstrated the value of transcuta- not be interpreted without additional information. The use
neous oxygen measurements as indices of perfusion or oxygen of near infrared spectroscopy to measure tissue hemoglobin
delivery. When PaO2 remains constant, a decrease in PtcO2 is oxygenationStO2 is a promising development, but one that
probably due to changes in perfusion. Changes in local perfu- requires further clinical study.

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oxygen monitoring during respiratory failure, cardiac decompensation,

CHAPTER 27 MINIMALLY INVASIVE


HEMODYNAMIC MONITORING
ANDREW J. GOODWIN, EDNAN K. BAJWA AND ATUL MALHOTRA

ity stems from the deleterious complications that are inherent


INTRODUCTION to an invasive procedure. Others have shown that even when
oxygen delivery in critically ill patients is known and is op-
The assessment of cardiac output (CO) has historically been timized or even increased to supranormal levels, there is no
vital to the management of critically ill patients. The underly- corresponding improvement in outcomes [10]. This gives rise
ing nature of shock in a hypotensive patient may not be obvious to the notion that once tissue hypoperfusion results in organ
clinically and is often multifactorial. In these circumstances, it dysfunction, a cycle of inflammation ensues which leads to
is crucial to characterize what type of shock (i.e., distributive, irreversible organ damage if not corrected early. This concept
cardiogenic, hypovolemic) is playing a role in a patients pre- has been described as cytopathic hypoxia where hypoperfu-
sentation as well as how they will respond to interventions, sion leads to the disruption of the intracellular utilization of
such as volume loading. Determination of CO is thought to be oxygen such that delivery of normal or supranormal amounts
a critical component of this process and thus has long been a of oxygen to a cell will not restore its function [11,12]. More
matter of interest to clinicians. recently, some intensivists have questioned the notion of cyto-
The physical exam can be unreliable in assessing hemo- pathic hypoxia although the concept of mitochondrial failure
dynamics in systolic heart failure [1] and in critically ill pa- in some ICU patients is relatively well accepted. Some data have
tients without recent myocardial infarction [2]. As such, more emerged that suggest that correction of hypoperfusion and in-
dependable measurements may be required to treat such pa- adequate oxygen delivery early in the course of sepsis improves
tients optimally. Since its introduction [3], the flow-directed outcomes [13,14]. Interestingly, these studies did not use PACs,
pulmonary artery catheter (PAC) has been useful in obtaining but instead used central venous oxygen saturation as a surro-
measurements of CO and has been used both diagnostically as gate for CO and oxygen utilization. Two other possibilities
well as to gauge response to treatment. For many years, the may explain the failure of RCTs to show benefit to the PAC.
PAC thermodilution technique was considered to be the gold Considerable data suggest inadequate knowledge among prac-
standard of ICU hemodynamic measurement. This philoso- titioners regarding the optimal use of PAC, making any hope
phy has been called into question over the last several years of improving outcome unlikely under such circumstances. Al-
in light of mounting evidence that clinicians may be using the ternatively, the failure of PAC trials may reflect failure of the
PAC ineffectively [4] and that morbidity and mortality in a va- protocols used to guide PAC treatment rather than failure of
riety of clinical situations are not improved with its use [57], the PAC per se [15].
but instead may be worsened [8,9]. Many are focusing on alternative and less invasive methods
In light of these studies, many clinicians have begun to ques- of determining cardiac function. These methods can be divided
tion the importance and the credibility of the PAC. Some pos- into two broad categories: measurements of cardiac function
tulate that the lack of improvement in morbidity and mortal- and measurements of indices of oxygen delivery and/or tissue
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246 Section II: Minimally Invasive Monitoring

perfusion as surrogates for CO. The goal of this research has cal usefulness of others is still unclear (partial carbon dioxide
been to develop feasible minimally invasive techniques that rebreathing).
provide accurate measurements in the ICU patient. In some
cases, these studies have focused on adapting monitoring tech-
nology that is already routinely used in this patient population. Esophageal Doppler
In this chapter, we focus on several emerging technologies
being used to determine CO and tissue perfusion in the ICU.
The methods of Doppler echocardiography, pulse contour anal-
Background
ysis, partial carbon dioxide rebreathing, and gastric tonometry To date, the esophageal Doppler (ED) has been one of the
represent the modalities best studied to date. Consideration most rigorously studied noninvasive CO measurement modal-
will also be given to new and developing methods such as sub- ities. Side et al. described ED in 1971 and it was later refined
lingual capnometry and biomarkers. Given its known limita- by Singer et al. [25,26]. This technique uses a Doppler probe
tions in critically ill patients, thoracic bioimpedance will not placed in the esophagus to measure blood flow in the descend-
be discussed in detail in this chapter. We will conclude with a ing thoracic aorta. The ED uses the Doppler Shift principle,
summary of practice recommendations and future directions. which implies that when a transmitted sound wave is impeded
by a structure, the reflected sound wave will vary in a frequency
dependent manner with the structures characteristics. In the
CARDIAC OUTPUT case of a fluid filled tube, such as the aorta, the magnitude
of Doppler shift will vary in direct proportion to the veloc-
CO is the amount of blood flow through the cardiovascular ity of flow in the tube (Fig. 27.1). Thus, the reflected sound
system over a period of time. Traditionally, it is reported in wave can be used to determine flow velocity in the descending
liters per minute and can be normalized for body surface area aorta. Multiplying this flow velocity by the ejection time and
to provide the cardiac index. In the normal subject, CO is di- the cross-sectional area of the aorta provides an estimate of
rectly related to a subjects metabolic rate and oxygen con- the stroke volume (SV). As this measurement does not account
sumption (VO2 ). The fundamental principles of CO will be for the component of total stroke volume that travels to the
described in more detail elsewhere in this text. The therapy for coronary, carotid, and subclavian arteries, a correction factor
a hypotensive patient with diminished CO (cardiogenic shock) must be applied to estimate the total SV. CO is then calculated
is fundamentally different from the therapy for a patient with by multiplying corrected stroke volume by the heart rate. The
diminished vascular tone (distributive shock). Therefore, an original versions of the ED system provided only Doppler shift
accurate knowledge of these variables is vital to the effective data; therefore, the cross-sectional area of the aorta was esti-
treatment of hypotension. The systemic vascular resistance is mated from a nomogram based on a patients height, weight,
calculated from the ratio of pressure gradient (mean arterial and age. Subsequently, a combined Doppler and ultrasound
pressure minus central venous pressure) to flow rate (CO). This probe has been introduced to provide estimates of both aortic
formula assumes an Ohmic resistor (i.e., one with a linear pres- flow velocity and cross-sectional area [27]. The descending aor-
sure flow relationship). Because a fall in systemic vascular re- tic cross-sectional area measured by this model correlated very
sistance could represent a decrease in blood pressure or a rise well with that measured by transesophageal echocardiography.
in CO, we favor the use of the primary measured variables in In addition, aortic blood flow measured with this model was
hemodynamic assessments. We would also suggest caution in well correlated with CO as measured by thermodilution [27].
the interpretation of changes in systemic vascular resistance Beyond providing an estimate of CO, ED systems can pro-
in isolation, without consideration for underlying mechanism vide information about the preload and the contractility of
(e.g., changes in CO). the heart. Singer et al. analyzed the flow-velocity waveform de-
Traditionally, a number of techniques have been used for rived from an ED system and discovered that the corrected flow
the assessment of cardiac function. Jugular venous pulsations, time (FTc ) correlated with preload [26,28] (Fig. 27.2). These
S3 gallop, and skin temperature have all been used to esti- studies further demonstrated that as preload was increased or
mate CO with mixed results [1618]. The pulmonary artery
occlusion pressure (PAOP) and central venous pressure (CVP)
have also been used as surrogates for left and right ventricular
function, respectively. The PAOP is commonly used to estab- Esophagus
lish the diagnosis of left heart failure in the hypotensive patient
and is often used to guide resuscitation. Magder et al. demon-
strated that the CVP could provide useful information about Probe
the volume status of critically ill patients [19,20]. Because the
majority of the blood volume is in the systemic veins, and the Aorta
right ventricle is the major determinant of CO, some would
Blood flow

argue that the CVP should receive more attention as the focus
of hemodynamic resuscitation protocols [21]. Unfortunately,
PAOP and CVP only represent the end-diastolic pressures of
their respective chambers. These variables do not always ac-
curately translate into systolic function and CO. In addition,
invasive assessment of PAOP [22,23] and clinical assessment of
CVP [24] have been notoriously difficult to assess accurately
and reliably.
Over the last few decades, considerable research has been
devoted to the accurate measurement of CO by minimally in-
vasive means. At present, there exist several modalities that
are able to provide estimates of CO on a continuous or near- FIGURE 27.1. Esophageal Doppler probe using the Doppler Shift
continuous basis. As described later, some have been estab- principle. Transmitted ultrasound waves are reflected back at vary-
lished enough to warrant increasing use in clinical settings ing frequencies, which depend on the velocity of flow of the red blood
(esophageal Doppler, pulse contour analysis) while the clini- cells they encounter.
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Chapter 27: Minimally Invasive Hemodynamic Monitoring 247

Peak velocity (cm/sec) TA B L E 2 7 . 1


ADVANTAGES AND DISADVANTAGES OF THE
ESOPHAGEAL DOPPLER SYSTEM FOR CARDIAC
OUTPUT MONITORING

Concept: Doppler probe in the esophagus measures stroke


volume in the descending aorta to estimate cardiac output.
Advantages
Continuous
Short set-up time
Low incidence of iatrogenic complications
Ability to leave in place for extended periods
Minimal training period required
Flow time (sec) Minimal infection risk
Stroke distance (cm) Disadvantages
Minute distance (stroke distance heart rate ) High up-front cost
Can only be used in the intubated patient
FIGURE 27.2. Esophageal Doppler flow-velocity waveform. May require frequent repositioning if patient is moved
(Adapted from Marik PE: Pulmonary artery catheterization and High interobserver variability
esophageal doppler monitoring in the ICU. Chest 116:10851091,
1999, with permission.)

decreased, the corrected flow time increased or decreased, re- probe can be placed in minutes and has been associated with a
spectively [26,28]. It is not clear, however, if following trends low incidence of major iatrogenic complications [3739]. Some
in FTc in response to volume loading is superior to following data suggest that once inserted, an esophageal probe can be left
trends to SV [29]. Wallmeyer et al. described a correlation be- in situ safely for more than 2 weeks [40]. One study determined
tween the peak velocity measured by Doppler and contractil- that the training required to become proficient in the use of ED
ity measured by electromagnetic catheter measured flow [30]. consisted of no more than 12 patients [41]. Furthermore, as the
Singer et al. further substantiated this finding by demonstrat- esophagus is a nonsterile environment, it is logical to assume
ing that dobutamine infusions increased peak flow velocities that the infectious risk of ED probe use is less than that of a
measured by an ED system in a dose-dependent fashion [31]. PAC placed percutaneously.
These observations suggest that an experienced operator may There are also technical disadvantages to the ED system.
be able to extrapolate useful hemodynamic parameters beyond One is the high up-front cost of the system itself as compared
the CO, through careful data synthesis. to the PAC apparatus. This cost may represent a very real lim-
itation in the number of systems that a facility can purchase
and maintain. This financial obstacle must be balanced with
Clinical Utility
the likelihood that multiple patients would have need of this
The clinical usefulness of the ED system is still being deter- system simultaneously, which would necessitate multiple sys-
mined. The majority of recent studies that have compared this tems. Another disadvantage of this system is that it can only
system to the gold standard of thermodilution have been per- be used in the intubated patient. Although a large percentage
formed in either intraoperative or postoperative settings and of critically ill and/or surgical patients who would benefit from
have revealed mixed results. One single-center study of 35 pa- this system fit this criterion, the nonintubated patient would
tients that compared ED measurements of CO to simultane- be more problematic. Additional concerns would include the
ous measurements of CO by thermodilution during off-pump likely need for repositioning or recalibration in the ICU patient.
coronary artery bypass graft showed very poor correlation be- Though surgical patients are often immobile, ICU patients are
tween the two techniques [32]. Other studies, including a meta- often repositioned frequently to prevent skin breakdown or to
analysis of 11 trials, have shown that ED systems are better at facilitate improved oxygenation. Such movements will increase
following changes in CO in response to fluid challenges than the chance of probe position changes that will require frequent
they are at measuring the absolute CO [3335]. The authors calibration and repositioning. Finally, Roeck et al. suggested
of the meta-analysis also made an important point when dis- that there is significant interobserver variability when measur-
cussing the reliability of comparing ED systems to thermodilu- ing changes in stroke volume in response to fluid challenges
tion. They argued that the poor reproducibility inherent in the with ED [35]. Poor reproducibility may limit the utility of this
thermodilution technique will likely affect the limits of agree- system.
ment between ED systems and thermodilution even if ED sys-
tems were reliable [33]. This concept was described by Bland Future Research
and Altman [36] and has important implications when com-
paring the accuracy of absolute CO measured by any system As the ED is used more widely, outcome data will be crucial. To
when compared to thermodilution. date, the majority of research has focused on the techniques va-
lidity and feasibility. One notable study which compared intra-
operative ED use with conventional monitoring during femoral
Advantages and Disadvantages neck fracture repair found a faster recovery time and signifi-
While comparing ED systems to thermodilution, technical ad- cantly shorter hospital stay in the ED group [42]. Similarly,
vantages and disadvantages deserve consideration (Table 27.1). Gan et al. demonstrated in a prospective randomized trial of
One advantage of the ED system is that it is continuous. Unlike patients undergoing major elective surgery that stroke volume
the traditional bolus thermodilution techniques, an ED system optimization using ED shortened hospital length of stay and
can continuously display CO, which allows earlier recognition resumption of PO intake as compared to conventional intra-
of hemodynamic deterioration or improvement in system re- operative care [43]. This latter finding may be due to less gut
sponsiveness to a therapeutic intervention. In addition, an ED hypoperfusion which has also been demonstrated with the use
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248 Section II: Minimally Invasive Monitoring

of ED [44]. A recent meta-analysis of nine trials of periopera- is used for calibration, a PAC is not necessary. When compared
tive ED use also found improvements in length of stay as well with pulmonary artery thermodilution, the arterial thermodi-
as time to resuming an oral diet [45]. lution method was found to be accurate, implying that it is an
Although the above-mentioned data suggest that periopera- acceptable method for calibration of a PCA system [4951].
tive outcomes are improved with the use of ED, there are no ro- More recently, a novel PCA system known as the Flotrac
bust parallel data for nonoperative ICU patients. The ultimate (Edwards Lifesciences, LLC, Irvine, CA) has been introduced.
use of ED will depend on further outcome data, availability of It is designed to autocalibrate on a continuous basis. It cal-
equipment and local experience and expertise. culates stroke volume using a general equation: SV = K pul-
satility, where K is a constant including arterial compliance
and vascular resistance [54]. This constant is initially derived
Pulse Contour Analysis by patient variables such as height, weight, sex, and age by
using a method described by Langewouters et al. [55] and is
subsequently adjusted once per minute using arterial waveform
Background characteristics. Pulsatility is determined by analyzing the stan-
Pulse Contour Analysis (PCA) is another modality for measur- dard deviation of the arterial pressure waveform over preceding
ing CO noninvasively that has been extensively studied. This 20-second intervals. Thus, the variables used to calculate SV
method relies on the theory, first described by Frank in the early are updated at least once per minute. This algorithm offers the
part of the twentieth century, that SV and CO can be derived advantage of not needing an alternative method for calculating
from the characteristics of an aortic pressure waveform [46]. CO for calibration purposes. When compared to pulmonary
Wesseling et al. eventually published in 1983 an algorithm to artery catheter thermodilution in a postcardiac surgery setting,
link mathematically SV and the pressure waveform [47]. This this system showed good correlation over a wide range of COs.
original version calculated SV continuously by dividing the area In addition, it appears that a radial artery catheter is just as
under the curve of the aortic pressure waveform by the aortic accurate as a femoral artery catheter in this setting, which is
impedance. As aortic impedance varies between patients, it had another advantage of this system [54].
to be measured using another modality to initially calibrate the
PCA system. The calibration method usually employed was Clinical Utility
arterial thermodilution. Aortic impedance, however, is not a
static property. It is based on the complex interaction of the As mentioned earlier, the initial trials studying PCA systems
resistive and compliant elements of each vascular bed, which used data from static ventricular loading conditions. Both the
are often dynamic, especially in hemodynamically unstable critically ill and the intraoperative patient, however, often ex-
patients. Since the first PCA algorithm was introduced, sev- perience rapid changes in ventricular preload. The accuracy
eral unique algorithms have been created to model accurately of the PiCCO system with dynamic changes in preload was
the properties of the human vascular system for use in PCA addressed in a subsequent study, which used a modified algo-
systems. rithm. Felbinger et al. showed that changes in CO in response
PCA involves the use of an arterial placed catheter with a to preload could be accurately measured in a cardiac surgical
pressure transducer, which can measure pressure tracings on ICU population when compared to pulmonary thermodilution
a beat-to-beat basis. Such catheters are now routinely used in [56].
operating rooms and ICUs as they provide a continuous mea- Although being able to monitor changes in CO during vol-
surement of blood pressure that is superior to intermittent non- ume loading is important, being able to predict a priori when
invasive measurements in hemodynamically unstable patients. a patient would benefit from volume loading is perhaps more
These catheters are interfaced with a PCA system, which uses useful. Pulse pressures commonly vary throughout the respira-
its unique algorithm as well as the initial aortic impedance cal- tory cycle. Pulse pressure variation (PPV) is defined as the result
ibration data from a thermodilution measurement of CO to of the minimum pulse pressure subtracted from the maximum
provide a continuously displayed measurement of CO. Obvi- pulse pressure divided by the mean of these two pressures.
ously, the reliability of a PCA system depends upon the accu-
racy of the algorithm that it employs. Because each algorithm Pulse Pressuremax Pulse Pressuremin
PPV = (1)
is unique in the weight that it ascribes to each element of vas- Pulse Pressuremean
cular conductivity, it is impossible to ensure that a system will
be able to reproduce the results of another system under simi- The magnitude of the PPV in a patient can predict preload
lar conditions [48]. Keeping this in mind, one cannot conclude responsiveness [5759]. Analogous to PPV, an additional piece
that all systems are equally reliable. of data that PCA systems can provide is the stroke volume vari-
PiCCO (Pulsion SG, Munich, Germany) is a PCA system ation (SVV). The SVV represents the change in percentage of
that has received considerable attention in the literature. Nu- SV over a preceding time period as a result of changes in SV
merous studies have demonstrated good correlation between due to ventilation. So far, the ability to use SVV to determine
this system and pulmonary thermodilution in both critically preload responsiveness has yielded mixed results. Reuter et al.
ill and surgical patients [4953]. Notably, this system did not found that SVV reliably decreased as cardiac index increased
require recalibration during these study periods, which were in response to preloading with colloids in ventilated postoper-
performed under static ventricular loading conditions. The sys- ative cardiac surgical patients [60]. This finding supports the
tem involves the placement of a femoral arterial catheter that argument that the magnitude of SVV may be used to predict
is passed into the abdominal aorta. In addition to a pressure preload responsiveness. It is important to note that the tidal
transducer, the catheter also contains a thermistor for arterial volumes used in this study were supraphysiologic (15 mL per
thermodilution. The system is calibrated by injecting cold saline kg), which results in a larger SVV and a resultant increase in the
via a central venous catheter at the right atrium in a manner accuracy of this approach. Subsequently, another study used a
similar to pulmonary arterial thermodilution. Instead of using smaller tidal volume (10 mL per kg) in a similar patient popula-
a thermistor in the pulmonary artery, however, the thermistor tion and could not demonstrate a reliable relationship between
on the femoral arterial catheter allows calculation of CO. This SVV and an increase in cardiac index in response to preloading
initial value of CO is then used to calibrate the PCA system that [61]. This finding suggests that when using lower tidal volume
is attached to the arterial catheter. Because the arterial catheter ventilation strategies, which are optimal for acute respiratory
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Chapter 27: Minimally Invasive Hemodynamic Monitoring 249

TA B L E 2 7 . 2
Partial Carbon Dioxide Rebreathing Method
ADVANTAGES AND DISADVANTAGES OF THE PULSE
CONTOUR ANALYSIS METHOD FOR CARDIAC Background
OUTPUT MONITORING
The Fick equation for calculating CO has been known for over
Concept: Arterial catheter used to determine stroke volume a 100 years. Its underlying principle states that for a gas (X)
from aortic pressure waveforms. whose uptake in the lung is transferred completely to the blood,
Advantages the ratio of that gass consumption (VX) to the difference be-
Continuous tween the arterial (Ca X) and venous (Cv X) contents of the gas
Uses catheters that are already commonly used in ICU will equal the CO. In its original form, Fick used the example
patients of oxygen (O2 ) and described the following equation:
Does not require calibration with pulmonary artery catheter VO2
Disadvantages Cardiac Output = (2)
Ca O2 Cv O2
Likely unable to determine preload responsiveness during
low tidal volume ventilation For this equation to be accurate, several conditions must
Questionable accuracy during large changes in blood exist. The first is that blood flow through the pulmonary capil-
pressure laries must be constant. In order for this to occur, the right and
Questionable accuracy during vasoconstrictor use left ventricular outputs must be equal (i.e., steady state) and
there must be no respiratory variation of pulmonary capillary
flow. Another condition critical to this methods accuracy is
an absence of shunts. As this method is dependent upon using
distress syndrome (ARDS), PCA-derived SVV should not be gas exchange to calculate CO, any blood that does not par-
used to estimate preload responsiveness. ticipate in gas exchange will result in underestimation of CO.
Furthermore, oxygen uptake by the lung itself must be minimal
to maintain the integrity of this equation.
Advantages and Disadvantages Although possible, the accurate measurement of VO2 is
Overall, the pulse contour analysis system offers several ad- clinically challenging, especially in patients who require high
vantages over the traditional gold standard of pulmonary FiO2 [64]. This prompted investigators to focus on using car-
artery thermodilution (Table 27.2). Depending on the system, bon dioxide production (VCO2 ) in place of VO2 [6567]. As
only an arterial catheter (Flotrac) or an arterial catheter and a VO2 is equal to VCO2 divided by the respiratory quotient,
central venous catheter (PiCCO) are required, both of which they determined that CO could be calculated by VCO2 divided
are commonly in place in critically ill and surgical patients. by the arteriovenous difference between O2 concentrations as
Thus, PACs and their possible risks can be avoided when us- well as the respiratory quotient (R). To measure O2 concentra-
ing these systems. The PCA systems also provide a continuous tions continuously, arterial and venous oximeters were used to
measurement of CO as opposed to the intermittent nature of measure oxygen saturation (SO2 ) and concentration was deter-
traditional thermodilution systems. mined based on measured hemoglobin (Hgb) levels. This tech-
As with any system, there are disadvantages to the PCA nique, therefore, relied upon the assumption that both R and
system as well. The ability to use this system to determine hemoglobin levels remained constant during the measurement
preload responsiveness is questionable in patients who are be- period.
ing managed with recommended ventilatory strategies. In ad-
VCO2
dition, some data suggest that in patients who have marked VO2 = (3)
changes in blood pressure, the algorithm is not able to model R
adequately the changes in vascular resistance and compliance Ca O2 = 13.4 Hgb Sa O2 (4)
and, therefore, the accuracy of the measured CO declines [62].
Furthermore, a similar breakdown in the accuracy of measured VCO2
CO = (5)
CO has been suggested during the administration of vasocon- 13.4 Hgb R [Sa O2 Sv O2 ]
strictors [63], which are common in the critically ill patient.
Using this method, one study found good correlation with
CO determined by thermodilution [67]. The drawback to this
Future Research
approach, however, is the need for an invasive central venous
The clinical utility of the pulse contour analysis system is still catheter to measure accurately venous oxygen saturations as
being determined. Future studies that may help in defining the well as initially to calibrate the system and determine R. Sub-
systems clinical role could focus on several points. First, a sequently, the partial carbon dioxide rebreathing method was
better understanding of how changes in blood pressure and introduced in an attempt to avoid the need for such catheters.
vasoconstrictor use affect the accuracy of a particular systems The partial CO2 rebreathing method is based upon the Fick
algorithm will help to determine when a system needs to be equation for CO2 [68]:
recalibrated to maintain its accuracy. In addition, an analy-
sis of how SVV predicts preload responsiveness at lower tidal
VCO 2
CO = (6)
volumes will provide more applicable information. Finally, a Cv CO2 Ca CO2
paucity of data regarding how PCA systems affect patient out-
comes exists at present. Comparisons between the outcomes When using this method, a disposable rebreathing loop is
seen with this system and pulmonary artery thermodilution placed between the endotracheal tube and the ventilator re-
may provide convincing evidence about the real usefulness of sulting in the rebreathing of carbon dioxide. A carbon diox-
PCA. In particular, the common question will the patient re- ide sensor, an airflow sensor, and an arterial noninvasive pulse
spond to fluids? may be replaced by the question should oximeter are then used to gather data before and after a period
the patient be given fluids? once adequate outcome data are of CO2 rebreathing. The CO2 sensor and airflow monitor allow
available. for the calculation of produced carbon dioxide (VCO 2 ) both
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250 Section II: Minimally Invasive Monitoring

before and during the rebreathing period. Because CO does not certain clinical situations as the accuracy of currently marketed
change from baseline during rebreathing conditions [69], one systems is improved.
can generate the following equation [68]: Determining which clinical situations are appropriate for
the partial rebreathing method is critical when considering its

VCO2
baseline use. Because the methods accuracy depends upon an estimate
CO =
Cv CO2 Ca CO2 of Ca CO2 from etCO2 as well as an estimate of shunt, clinical
baseline baseline
situations that affect these estimates may not be appropriate

VCO2 for using this method. For instance, post-operative cardiac sur-
rebreathing
= gical patients tend to have increased pulmonary dead space
Cv CO2 Ca CO2 and shunt [77] and may not be an appropriate population for
rebreathing rebreathing
partial CO2 rebreathing monitor use [76]. In addition, some
(7) data suggest that the correlation between this method and ther-
Gedeon et al. [70] determined that subtracting the rebreath- modilution declines as the amount of venous admixture from
ing ratio from the baseline ratio yields the following equation shunting increases in animal models [78]. In order for Ca CO2
[68]: to be estimated accurately by etCO2 , gas exchange needs to be
somewhat homogenous throughout the lung. One of the hall-
CO = marks of acute lung injury (ALI) and ARDS is a heterogeneous

VCO2 VCO
2 pattern of injury and fibrosis. This heterogeneity results in a
baseline rebreathing
    large variation of gas exchange throughout the lung. Conse-
Cv CO2 Ca CO2 Cv CO2 Ca CO2 quently, the etCO2 may be a poor estimate of Ca CO2 leading
baseline baseline rebreathing rebreathing
to an important source of error. Indeed, one study, which com-
(8)
pared the partial CO2 rebreathing method to thermodilution in
As CO2 diffuses rapidly into the blood, one can further as- patients with varying degrees of ALI, found poor agreement be-
sume that the mixed venous CO2 concentration (Cv CO2 ) re- tween the two methods [79]. The disagreement intensified with
mains unchanged between baseline and rebreathing conditions, worsening severity of ALI. Finally, significant variations in tidal
that is, Cv CO2 = Cv CO2 . This allows for fur- volume during a period of measurement will often markedly
baseline rebreathing
affect the accuracy of VCO2 on a breath-to-breath basis. Con-
ther simplification of the equation to the following [68]:
sequently, the accuracy of measured CO is limited in situations

VCO 2
of varying tidal volume such as pressure support ventilation
CO = (9) [80].
Ca CO2
Ca CO2 can be estimated from end-tidal carbon dioxide
(etCO2 ) and the carbon dioxide dissociation curve. Therefore, Advantages and Disadvantages
Ca CO2 can be substituted for by etCO2 multiplied by the The most notable advantage of the partial CO2 rebreathing
slope (S) of the dissociation curve [68]: method is its true noninvasive nature. With the exception of the
arterial blood gases used to estimate shunt, this method does
VCO 2
CO = (10) not require any additional invasive procedures. In addition,
etCO2 S CO can be measured on a near-continuous basis. However, the
An estimate of CO can now be calculated using data that disadvantages of the system are substantial (Table 27.3). It is
can be measured before and after a period of rebreathing, in challenging to use in patients who are not intubated or in in-
addition to S, which can be determined from a carbon dioxide tubated patients with spontaneous ventilation. Its accuracy is
dissociation curve. It is important to note that the estimate of questionable in patients with intrapulmonary shunt and lung
CO calculated using equation 10 only accounts for the blood injury, which are both common findings in the ICU. Because the
that is able to participate in gas exchange. Any blood involved technique raises arterial PCO2 , its safety in patients with hy-
in a right to left intrapulmonary shunt is not considered by this percapnia or increased intracranial pressure is unknown. Each
equation; therefore, a correction factor must be incorporated system also represents an important fixed cost but can only
to account for this shunted blood. This is determined by a be used by one patient at any given time. The limited clinical
partial rebreathing system by using the data collected from utility of these systems may not justify this expenditure.
the noninvasive arterial oximeter, the FiO2 , and the PaO2 as
determined by arterial blood gases. These data allow one to
determine an estimate of shunted blood using Nunns iso-shunt
tables [71]. TA B L E 2 7 . 3
ADVANTAGES AND DISADVANTAGES OF THE
Clinical Utility PARTIAL CARBON DIOXIDE REBREATHING METHOD
So far, the results of comparisons between partial CO2 re- FOR CARDIAC OUTPUT MONITORING
breathing techniques and alternative methods of measuring
CO have been mixed at best. Although some studies have Concept: Using exhaled carbon dioxide to determine cardiac
demonstrated reasonable agreement with the gold standard output using a modified Fick equation
of thermodilution [7274], others have shown poor agreement Advantages
[52,75,76]. One of these studies [76] did demonstrate good re- Truly noninvasive
producibility of the results obtained from the partial rebreath- Nearly continuous
ing method despite the fact that they did not correlate with Disadvantages
results obtained by thermodilution. One could infer from this High up-front cost
that the method may have been appropriately precise but that Can only be used in the intubated patient
something in its algorithm, that is, estimation of shunt or es- Questionable accuracy in patients with lung injury
timation of Ca CO2 from etCO2 , prevented it from obtaining Unclear risk in patients with hypercapnia or increased
accurate results. This may be encouraging evidence that the intracranial pressure
partial rebreathing method can be an acceptable technique in
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Chapter 27: Minimally Invasive Hemodynamic Monitoring 251

Future Research Tissue levels of CO2 rise early in the setting of hypoperfusion
[8789]. The level of CO2 in a tissue is determined by the bal-
At present, the clinical applicability of partial CO2 rebreathing
ance between the concentration of arterial CO2 (Ca CO2 ), blood
systems is not completely known. Future research should focus
flow to the tissue, and CO2 production by the tissue. In a state
on further examining the accuracy of these systems in patients
of hypoperfusion, CO2 increase is thought to be multifactorial.
with lung injury as the current data are limited. Improvements
Carbon dioxide production increases in hypoperfused tissue to
of existing algorithms for shunt and Ca CO2 estimation could
buffer the increase in hydrogen ions generated by the hydrol-
also aid in increasing this methods generalizability. Finally, de-
ysis of ATP during glycolysis [90]. In addition, the low flow
termining if this methods noninvasive nature truly makes a
state seen in hypoperfusion results in an impaired clearance of
difference in clinical outcomes should be an important focus
CO2 causing a further increase in tissue CO2 concentrations
of upcoming investigation. In critically ill patients, there may be
[91]. This impaired clearance is likely the largest contributor
no major advantage to using monitoring techniques that avoid
to tissue hypercapnia in states of hypoperfusion [92]. The com-
central lines and arterial lines since these are nearly ubiquitous
plex mucosal circulation of the gut results in the recirculation
in the ICU.
of CO2 as well as arteriovenous O2 shunting, which is exacer-
bated by the low-flow state of hypoperfusion. As a result, the
gut mucosa is one of the earliest regions in the body affected
OXYGEN DELIVERY AND by hypoperfusion. This characteristic combined with the rela-
TISSUE PERFUSION tively easy accessibility of the gut makes gastric tonometry an
appealing choice for the early detection of shock [93].
Although directly measuring CO can provide information vital Tonometry is based on the principle that gases will equili-
to the management of critically ill patients, one can also argue brate between semipermeable compartments over time. Gastric
that accurate knowledge of oxygen delivery and/or adequacy tonometry involves placing a nasogastric tube tipped with a
of tissue perfusion can be similarly useful. Proponents of this fluid or air filled balloon into the lumen of the stomach and al-
concept are less interested in the absolute CO as long as ad- lowing its contents to equilibrate with the fluid in the stomach.
equate oxygen is delivered to tissues. One of the traditional This gastric fluid, in turn, is in equilibrium with the mucosal
techniques used to assess oxygen delivery is the mixed venous lining the stomach. Therefore, by sampling the steady state con-
oxygen saturation (Smv O2 ). The Smv O2 is measured by sampling tents of the balloon, one can estimate the partial pressure of
blood from the pulmonary artery, which is representative of the CO2 in the gastric mucosa (Pgm CO2 ). The original set-ups used
venous return from both the superior and inferior vena cava saline in the balloon, which required approximately 90 minutes
after sufficient mixing. Smv O2 is dependent on both systemic for equilibration. Once equilibrated, the saline was aspirated
oxygen delivery (DO2 ) as well as systemic oxygen consump- and its PCO2 was determined. Newer automated models use air
2 ). Because VO2 does not dramatically change in the
tion (VO in place of saline, which results in shorter equilibration times
absence of major metabolic derangements, decreases in Smv O2 (less than 20 minutes) and improved precision [9496]. Many
can be considered to be due to decreases in DO2 (and, thereby, of the early studies performed with gastric tonometry used the
CO) in many patients. As a result, investigators have focused Pgm CO2 to determine the intramucosal pH (pHi ) by estimat-
on the clinical utility of measuring Smv O2 as a surrogate means ing the tissue bicarbonate levels from serum bicarbonate and
of monitoring CO [81,82]. Pearson et al. found that Smv O2 solving the HendersonHasselbach equation. Recent focus has
monitoring did not improve length of ICU stay or length of shifted away from this approach due to the introduction of
vasopressor requirement when compared to traditional pul- error by estimating intramucosal bicarbonate from serum bi-
monary artery catheter use and CVP monitoring. In addition, carbonate. Instead, the PCO2 gap (Pgm CO2 Pa CO2 ) has been
Smv O2 monitoring cost more [83]. proposed as an alternative measure of tissue perfusion that is
Another potential drawback of Smv O2 monitoring is the less influenced by the systemic acidbase status [97].
need for PAC and the possible associated risks. Because many
critically ill patients receive central venous catheters, some re- Clinical Utility
search has focused on using central venous oxygen saturations
(Scv O2 ) rather than Smv O2 . One early study found that Scv O2 Given its relatively noninvasive nature, gastric tonometry
tended to be approximately 5% to 10% lower than Smv O2 in would be an ideal candidate for a safe modality for the guidance
humans [84]. While studying dogs, Reinhart et al. found good of resuscitation in shock. Indeed, many studies have attempted
correlation (r = 0.96) between the two [85]. So far, clinical to explore this techniques ability to guide therapy in situations
data using this variable are limited, however, the previously of hypoperfusion. Silva et al. measured changes in PCO2 gap
mentioned landmark trial by Rivers et al. used Scv O2 among in addition to changes in systemic hemodynamic variables in
other variables with success [13,14]. response to fluid challenges in septic patients. They found that
In addition to estimating oxygen delivery, recent research while cardiac index increased in response to fluid loading, in-
has focused on estimating tissue perfusion as a guide for resus- dices of global oxygen delivery such as Smv O2 did not. The
citative therapy. With this approach, the adequacy of blood and PCO2 gap, however, was noted to significantly fall in response
oxygen delivery is assessed by measuring markers of hypoper- to fluid challenges [98]. This implies that gastric tonometry
fusion of accessible organs. We will focus on three modalities may provide a more reliable and less invasive means of mon-
that have demonstrated considerable promise in this field to itoring response to resuscitation than monitoring traditional
date: gastric tonometry, sublingual capnometry, and cardiac global variables of oxygenation such as Smv O2 . Jeng et al. mon-
biomarkers. itored Pgm CO2 in a small series of burn patients and found that
changes in Pgm CO2 often preceded more traditional signs of
hypoperfusion such as changes in mean arterial pressure and
Gastric Tonometry urine output [99].
In perhaps the best-known trial using this modality, Gui-
tierrez et al. randomized 260 critically ill patients in the ICU
Background to a standard therapy arm and a protocol arm in which pa-
Mounting evidence that early correction of hypoperfusion in tients received additional therapy aimed at improving oxygen
shock improves mortality [13,14,86] has led investigators to delivery whenever pHi fell below 7.35 [100]. These authors
focus on the development of methods for its early detection. found a significant increase in 28-day survival in a subset of the
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252 Section II: Minimally Invasive Monitoring

protocol group whose pHi was greater than 7.35 on admission. TA B L E 2 7 . 4


Although this study suggested that gastric tonometry could be
used to improve survival in a select group of patients, perhaps ADVANTAGES AND DISADVANTAGES OF GASTRIC
its most relevant point is that early correction of hypoperfusion TONOMETRY
is crucial to improving survival. Barquist et al. compared the
effects of a pHi guided splanchnic therapy with that of a non- Concept: Using a semipermeable balloon in the lumen of the
pHi guided therapy in trauma patients. They found that pa- stomach to estimate gastric mucosal perfusion
tients in the splanchnic therapy group had fewer organ failures, Advantages
which was associated with shorter length of both ICU and hos- Low risk of infection
pital stays [101]. Unfortunately, a similar splanchnic-oriented May provide signs of early shock before traditional methods
therapy failed to show significant clinical benefit when com- Provides evidence of response to therapy before traditional
pared to conventional therapy in trauma patients in a more markers
recent study [102]. Disadvantages
Not all studies, however, have demonstrated the usefulness Not continuous, takes up to 20 min per measurement
of gastric tonometry as a resuscitative guide. In one notable Does not reveal the cause of hypoperfusion (i.e., cardiogenic
article comparing pHi -guided therapy with therapy guided vs. distributive)
by global oxygen delivery indices in trauma patients, Ivatury
et al. did not find any significant difference in overall mortal-
ity [103]. In their analysis, however, they pointed out that the
time to optimization of pHi was significantly longer in nonsur- in intravascular volume more closely [114]. One major concern
vivors. This implies that the resuscitative therapy used or the for this modality is its inability to accurately measure Pgm CO2
clinical condition of the nonsurvivors likely resulted in a delay during enteral feeding. This may limit gastric tonometrys use
of pHi optimization and that this delay was most responsible in patients with protracted critical illness.
for their outcome. Gomersall et al. also compared pHi -guided
therapy with conventional treatment in 210 ICU patients [104].
Future Research
They, too, found no significant change in mortality although
this study may have been underpowered [105]. The future study of gastric tonometry should focus in several
Although the ideal use of gastric tonometry is guidance directions. First, it should be used to help determine effective
of resuscitation in shock, many studies using this modality protocols for increasing gut mucosal perfusion. Poorly out-
have demonstrated its prognostic utility. Levy et al. analyzed lined and/or ineffective protocols were potential flaws in both
how pHi and PCO2 gap on admission to the ICU and at 24 the Guitierrez and the Ivatury studies [100,103]. A clearly de-
hours correlated with outcome in 95 critically ill patients [86]. lineated and effective protocol for optimizing pHi or PCO2 gap
They found that the nonsurvivor group had significantly lower would allow for a more meaningful comparison between con-
pHi values on admission and at 24 hours as compared to the ventional and gastric-tonometryguided treatment. Further-
survivor group. In addition, the PCO2 gap at 24 hours inde- more, once a reliable protocol has been determined, gastric
pendently predicted 28-day survival. These findings supported tonometry may be used to validate further the increasing evi-
those of Maynard et al. who compared pHi with other global dence that early restoration of perfusion and oxygen delivery
measures of perfusion in 83 patients with acute circulatory fail- in shock is crucial to outcomes. Finally, the ability of gastric
ure. In their study, pHi was found to be a better predictor of tonometry to predict not only mortality but also ability to wean
outcome than lactate and other global measures of perfusion from mechanical ventilation should be further explored as this
[106]. Interestingly, mortality may not be the only outcome that may help to guide determining goals of care and family decision
can be predicted through the use of gastric tonometry. Lebuffe making.
et al. demonstrated that the intraoperative gap between gastric
and end-tidal CO2 can predict postoperative morbidity in high-
risk patients undergoing major surgery [107]. The relationship Sublingual Capnometry
between pHi and outcome of ventilator weaning has also been
studied [108111]. In these studies, a low baseline pHi and a
significant drop in pHi during weaning were associated with
Background
failure to wean and failed extubations. It is not entirely clear if In attempts to further explore the clinical utility of guiding
the witnessed drop in pHi is due to splanchnic ischemia from resuscitative therapy by tissue CO2 levels, investigators have
diverted blood flow to facilitate increased work of breathing begun to focus on using alternative sites for measurement. One
or if it is related to increased Pa CO2 . site that appears to be particularly promising due to its easy
Thus far, studies have suggested that gastric tonometry may accessibility and, thus far, its accuracy, is the sublingual mu-
be a promising modality for the treatment and prognosis of cosa. After Sato et al. demonstrated that esophageal pHi cor-
shock with numerous advantages over traditional methods related well with gastric pHi in a rodent model [115], Jin re-
(Table 27.4). It is relatively noninvasive and can provide early vealed that the more proximal sublingual mucosa developed
information regarding the development of hypoperfusion that hypercapnia to a similar degree as gastric mucosa in a model
may be more reliable than global indices of oxygen delivery. of hemorrhagic shock [116]. These authors went on to show
Insufficient sample sizes and the inability of some treatment not only a close correlation between increases in sublingual
protocols to raise pHi may explain some of the negative re- PCO2 (Psl CO2 ) and decreases in arterial pressure and cardiac
sults derived from the studies performed to date. Critics of this index [117] but also demonstrated that reversal of shock led to
modality question the validity of using gastric intramucosal pH a correction of Psl CO2 comparable to that of Pgm CO2 and more
as a surrogate for the entire splanchnic circulation [112]. Oth- rapidly than the traditional marker of hypoperfusion, lactate
ers wonder if the information obtained from gastric tonometry [118].
could be determined less invasively by the base deficit/excess The most widely clinically studied sublingual capnometry
[113]. This particular question was partially addressed by To- system is the Capnoprobe SL Monitoring System (Nellcor;
tapally who showed that base excess responded very slowly to Pleasanton, CA) which is a CO2 -sensing optode. This device
changes in intravascular changes in hemorrhagic shock in rats. is a CO2 -permeable capsule filled with a buffered solution of
Alternatively, esophageal PCO2 gap was seen to reflect changes fluorescent dye. The capsule is attached to an optic fiber and
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Chapter 27: Minimally Invasive Hemodynamic Monitoring 253

is placed under the tongue. As CO2 diffuses into the capsule, of cardiac biomarkers in the ICU setting is becoming an in-
the pH of the buffered solution is altered by production of creasingly popular method of determining early cardiac dys-
carbonic acid (H2 CO3 ). This change in pH results in an al- function. As they can be obtained from a peripheral venous
teration of the fluorescent emissions from the solution, which blood sample, they represent completely noninvasive and po-
is ultimately sensed as a change in projected light by the at- tentially valuable data that may assist in prognostication as
tached optic fiber. Hence, by calibrating wavelengths of light well as in guiding management. To date, research has focused
with known partial pressures of CO2 , one can measure PCO2 primarily on two proteins: troponin and B-type natriuretic pep-
with this system. To ensure the highest possible accuracy of the tide (BNP).
device, it must be placed securely under the tongue with the
mouth closed. An open mouth allows the entrance of light and Troponin
ambient air to the optode, which can significantly alter accu-
Troponin T (TnT) and Troponin I (TnI) are cardiac-specific
racy. The reliable range of a well-seated and calibrated probe
contractile proteins that have been studied extensively in the
is 30 to 150 mm Hg [119].
context of myocardial ischemia. Both have been shown to be
superior to the traditional creatinine kinase MB (CK-MB) in
Clinical Utility diagnosing myocardial injury in certain clinical contexts [125
Using this probe, researchers began to further investigate the 127]. As such, they have become part of the mainstay for diag-
comparability of sublingual capnometry and gastric tonometry nosing acute myocardial infarction today. Less is known about
as well as the clinical utility of capnometry. In one validation their role in the ICU in patients who are not undergoing my-
study, Marik demonstrated close correlation between Pgm CO2 ocardial infarction due to coronary plaque rupture. Several
and Psl CO2 (r = 0.78; p < 0.001) in a heterogeneous popula- authors have observed an elevated level of troponin in ICU
tion of 76 ICU patients [120]. Furthermore, Marik and Bankov patients who are not undergoing an acute coronary syndrome
went on to show that in another ICU population of 54 pa- [128,129]. One recent prospective case control study showed
tients, Psl CO2 and Psl CO2 Pa CO2 gap were better predictors that 17 out of 20 patients (85%) with systemic inflammatory
of outcome than lactate or Smv O2 . These authors specifically response syndrome (SIRS), sepsis, or septic shock had eleva-
found that a Psl CO2 Pa CO2 gap greater than 25 mm Hg was tions in TnI. Furthermore, of the six patients who died in the
the best discriminator of outcome. In addition, they found that study, five had elevated TnI levels. Ten of the seventeen patients
Psl CO2 and Psl CO2 Pa CO2 gap were more responsive to treat- with elevated TnI levels had no evidence of important coronary
ment measures than were lactate and Smv O2 [121]. Weil et al. artery disease by coronary angiography, stress echocardiogra-
also demonstrated the prognostic abilities of sublingual cap- phy, or autopsy [130]. Interestingly, in this study there were
nometry when they found that a Psl CO2 <70 mm Hg had a patients with a normal LVEF by echocardiography who had in-
positive predictive value of 93% for survival [122]. creased TnI levels. This suggests that TnI may be able to detect
Unfortunately, in 2004 Nellcor initiated a voluntary recall myocardial dysfunction even when echocardiography cannot.
of the Capnoprobe device after reports of Burkholderia cepa- Troponin has also been studied as a prognostic marker in sep-
cia being cultured from patients using this device as well as sis. Spies et al. measured serum TnT levels in 26 septic patients
from unused devices themselves. As such, there is currently in a surgical ICU. They found that elevated TnT levels within
no system commercially available for sublingual capnography. the first 24 hours of sepsis were associated with a significantly
Further insight into its clinical utility will have to wait until higher mortality rate when compared to normal TnT levels
this technology is again available for clinical use. [131]. Thus, troponin may be useful for detection of occult
myocardial dysfunction as well as for prognostication in ICU
Conclusion patients in the absence of an acute coronary syndrome. These
promising early findings as well as the development of more
In summary, the existing research regarding the clinical utility sensitive troponin assays [132] should lead to further research
of sublingual capnometry appears promising. This technique into the utility of troponin in the ICU.
may provide similar accuracy to gastric tonometry while being
less invasive and providing results on a more instantaneous BNP
basis. In addition, it does not require discontinuation of enteral
feeding during measurement periods, as some have advocated The natriuretic peptides are a family of hormones that exert
for gastric tonometry. If sublingual capnography is safely made a wide range of biologic functions including diuresis and va-
available again, it may replace the use of lactate and Smv O2 as sodilation. Two members of this family, atrial natriuretic pep-
markers of hypoperfusion and as resuscitative guides. Further tide (ANP) and B-type (or brain) natriuretic peptide (BNP),
research into this techniques effect on patient outcome would are secreted by the atria and the ventricles, respectively. Their
also be warranted in the future. secretion is stimulated by myocardial stretch induced by in-
creased filling volumes. Each hormone is derived from a
prohormone that is cleaved into the biologically active C-
Cardiac Biomarkers terminal component and the biologically quiescent but longer
lasting N-terminal component. In recent years, research has
suggested that BNP can be a valuable surrogate for left ventric-
Background ular end-diastolic pressure and left ventricular ejection fraction
Cardiac biomarkers are molecules, usually proteins, which are and can correlate with New York Heart Association heart fail-
specifically released from the heart into the blood and can be ure class in patients with congestive heart failure (CHF) [133
used to judge both cardiac function and dysfunction. Myocar- 137]. Until recently, however, little was known about the role
dial dysfunction is commonly seen early in the course of sepsis of BNP as a marker of myocardial dysfunction in the critically
[123] and may be related to elevated levels of proinflammatory ill population. Prompted by data that suggest that BNP can
cytokines such as interleukin-1 and tumor necrosis factor-, correlate with pulmonary artery occlusion pressure (PAOP)
which have been shown to be cardiodepressant [124]. How- in patients with severe CHF [138,139], Tung et al. investi-
ever, due to a concomitant increase in left ventricular ejection gated the utility of using BNP as a surrogate for pulmonary
fraction (LVEF) caused by afterload reduction from systemic artery catheter placement in a heterogeneous population in
vasodilation, diagnosis of myocardial dysfunction early in sep- shock. Although BNP levels did not correlate with cardiac in-
sis can be difficult by traditional echocardiography. The study dex or PAOP in this study, they did find that a BNP level of
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254 Section II: Minimally Invasive Monitoring

<350 pg per mL had a 95% negative predictive value for the di- TA B L E 2 7 . 5
agnosis of cardiogenic shock [140]. This suggests that although
BNP should not be used in place of PAOP, a low BNP level may SUMMARY OF RECOMMENDATIONS BASED ON
obviate the need for PAC placement. RANDOMIZED CONTROLLED CLINICAL TRIALS
This study also demonstrated that BNP levels have prognos-
tic significance among the critically ill. The median BNP level at Early intervention in shock is beneficial
the time of PAC placement was significantly higher in the non- Esophageal Doppler can be used to follow trends in cardiac
survivor population as compared with survivors. In addition, a output
multivariate analysis showed that a BNP concentration in the Pulse contour analysis can reliably estimate cardiac output
highest log-quartile was the strongest predictor of mortality in perioperative patients
with an odds ratio of 4.5. This was an even stronger predictor Stroke volume variation cannot reliably be used to estimate
of mortality than the APACHE II scores [140]. The prognos- preload responsiveness during low tidal volume ventilation
tic utility of BNP was further validated by Brueckmann et al.
when these authors found that elevated N-terminal proBNP
(NT-proBNP) levels on day 2 were significantly correlated with
an increased mortality rate in patients with severe sepsis. These arguably, the most important variable to follow. Alternatively,
authors did not, however, find prognostic significance with N- gastric tonometry, and by extension sublingual capnometry, do
terminal proANP (NT-proANP). Interestingly, the levels of NT- not focus on the absolute CO but instead measure indices of
proBNP, NT-proANP, and troponin I were all found to be sig- tissue perfusion. This quality combined with noninvasiveness,
nificantly lower in patients being treated with drotrecogin alfa makes these techniques appealing as replacements of thermod-
(activated) than in those not receiving it [141]. This suggests ilution. The partial carbon dioxide rebreathing method has
that drotrecogin alfa (activated) may provide some cardiopro- not yet sufficiently demonstrated its applicability to the crit-
tective effect in severe sepsis, perhaps through its proposed ically ill patient. Confounding clinical features such as ALI are
anti-inflammatory properties [142]. However, the sample size commonly found in this population and would likely impair
did not allow assessment of mortality benefit from APC. the validity of existing systems. Finally, although BNP has not
shown the ability to replace the PAC to date, there is some evi-
dence that suggests that patients with a low BNP may not need
Conclusion
one for diagnostic purposes. At present, use of any of these
In summary, the study of cardiac biomarkers in the ICU is still modalities must be performed cautiously. The majority of data
in the early stages. Till date, the majority of data suggests that available regarding these techniques has focused on comparing
troponin and BNP may have some prognostic significance in their accuracy with that of thermodilution. Few studies have
critically ill patients without CHF. Neither has been shown addressed patient outcomes. Ultimately, before definite recom-
to be able to guide management, so far, although some data mendations can be made, further research focusing on clinical
suggest that low BNP levels may exclude cardiogenic shock outcomes will be necessary.
thereby preventing the need for a diagnostic PA line. Larger
trials may further prove this concept in the future allowing for
less invasive management of a select population of patients.
Furthermore, a better understanding of the effect of drotreco-
FUTURE DIRECTIONS
gin alfa (activated) on cardiac biomarkers may provide some As medical technology continues to advance at an explosive
insight into the nature of the myocardial dysfunction seen in rate, it is easy to imagine that ICU practice will completely
sepsis. change in the not too distant future. The next generation of in-
tensivists and likely younger members of this generation may
find themselves looking back with awe at the archaic meth-
PRACTICE RECOMMENDATIONS ods of current practice. At present, there are many technologies
that are still in their early stages but may one day provide useful
Independent of which cardiac monitoring technique is em- clinical information. A few of these deserve mention.
ployed, a strategy that should be utilized in all patients with Magnetic resonance imaging (MRI) has become a common
shock is early intervention. Mounting evidence suggests that fixture in many large hospitals and is routinely used in a variety
mitochondrial failure may play a role in late shock [11,12] of clinical settings due to its improved accuracy over computed
and efforts to correct hemodynamic derangements and aug- tomography (CT) in defining soft tissue structure. The role of
ment oxygen delivery early in shock have shown promising MRI continues to expand as clinicians and researchers develop
results, thus far [13]. The optimal method for cardiac monitor- new ways to use its capabilities. One area in which MRI has
ing, however, is yet to be determined. At present, pulmonary shown particular promise is that of cardiac MRI. Although this
artery thermodilution remains the gold standard; however, technique is still being primarily used experimentally, early re-
increasing interest has been given to less invasive monitoring sults have demonstrated its ability to assess both cardiac func-
modalities. Till date, the most substantial research has focused tion as well as viability [143145]. As more data become avail-
on ED, pulse contour analysis (Table 27.5), and gastric tonome- able, one can envision the possibility of more routine use of
try systems. Although there remains some question whether the MRI to assess cardiac function in the ICU. In addition, ad-
absolute CO determined by ED is accurate, most studies have vances in nuclear magnetic resonance (NMR) spectroscopy
proven its reliability in monitoring trends in CO in response to have made it possible to estimate arterial oxygen supply (DO2 )
therapeutic interventions. This ability to monitor trends may as well as skeletal muscle reoxygenation, mitochondrial ATP
be sufficient for the management of patients in shock. Pulse production, and oxygen consumption(VO2 ) [146]. Although
contour analysis systems have also proven to be useful in mon- cost and the technical difficulties of using MRI in the ICU may
itoring trends in response to interventions. In addition, PCA be prohibitive, there clearly exists potential in this arena.
systems do not require additional invasive procedures other Although traditional two-dimensional transthoracic echo-
than an arterial catheter, which is commonly used in patients cardiography is certainly not a new technology, recently there
with shock. has been new interest in this technique among intensivists.
Despite these positive attributes, both ED and PCA systems Echocardiography has historically fallen under the domain of
do not provide a direct measure of tissue perfusion, which is, cardiologists who are formally trained to perform and interpret
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Chapter 27: Minimally Invasive Hemodynamic Monitoring 255

these useful studies. This technique can provide a wealth of in- through insights gained in the fields of proteomics, genomics,
formation about systolic function, valvular dysfunction and and metabolomics. These techniques use next-generation tech-
pericardial disease in critically ill patients [147]. More and nologies of mass spectroscopy and microarray analysis to iso-
more, noncardiology intensivists are now learning how to per- late and compare which proteins, genes, and other molecular
form, at least, basic exams to help quickly guide initial man- markers are preferentially expressed during different disease
agement decisions. For example, some bedside ultrasound de- states. Through analysis of these patterns, it may be possible
vices used for central line placement, also have probes, which to better understand the mechanisms behind diseases such as
allow at least cursory examination of cardiac function (e.g., sepsis and ARDS. Ultimately such technologies could theoret-
to exclude pericardial tamponade). However, the authors are ically be used in the field of hemodynamic monitoring if such
aware of instances of erroneous information being gathered patterns could be associated with specific hemodynamic states.
from such devices when used in untrained hands. Therefore, Ideally, for example, a simple blood or urine test could re-
a more formal education in echocardiography would likely be veal a biomarker pattern consistent with cardiogenic shock that
beneficial for intensivists who do not have access to immediate would take the place of invasive measuring of CO. Determin-
echocardiography by an expert. ing these expression patterns as well as refining the technique
Finally, as in other areas of medicine, in the coming years such that the information could be obtained in a timely manner
emerging technology may substantially impact critical care will be important and challenging obstacles to overcome.

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traluminal PCO2 during weaning from mechanical ventilation. Crit Care community screening for left ventricular hypertrophy and systolic dysfunc-
Med 29(1):7076, 2001. tion: the Framingham heart study. JAMA 288(10):12521259, 2002.
112. Uusaro A, Lahtinen P, Parviainen I, et al: gastric mucosal end-tidal PCO2 138. Kazanegra R, Cheng V, Garcia A, et al: A rapid test for B-type natri-
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7(1):7984, 2003. 140. Tung RH, Garcia C, Morss AM, et al: Utility of B-type natriuretic peptide
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117. Nakagawa Y, Weil MH, Tang W, et al: Sublingual capnometry for diagnosis 142. Nacira S, Meziani F, Dessebe O, et al: Activated protein C improves
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and gastric tonometry during hemorrhagic shock [see comment]. Chest 143. Lee VS, Resnick D, Tiu SS, et al: MR imaging evaluation of myocardial
118(4):11271132, 2000. viability in the setting of equivocal SPECT results with (99 m) tc sestamibi.
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121. Marik PE, Bankov A: Sublingual capnometry versus traditional markers of 145. Kitagawa K, Sakuma H, Hirano T, et al: Acute myocardial infarc-
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258 Section II: Minimally Invasive Monitoring

CHAPTER 28 NEUROLOGIC MULTIMODAL


MONITORING
RAPHAEL A. CARANDANG, WILEY R. HALL AND DONALD S. PROUGH

Neurologic function is a major determinant of quality of life. ties to use, and that determining the most beneficial application
Injury or dysfunction can have a profound effect on a patients of these technologies requires further prospective study.
ability to be alert, communicate, and interact with his or her The compelling theoretical importance of brain monitoring
environment meaningfully, and function as an independent hu- is based on the high vulnerability of the brain to hypoxic and
man being. The brain is a highly complex organ with special- ischemic injuries. The brain uses more oxygen and glucose per
ized areas of function and is exquisitely sensitive to metabolic weight of tissue than any large organ, yet has no appreciable
and physical insults such as hypoxemia, acidosis, trauma, and reserves of oxygen or glucose. The brain is thus completely de-
hypoperfusion. The goal of neurocritical care is to protect pendent on uninterrupted cerebral blood flow (CBF) to supply
the brain and preserve neurologic functions in the critically ill metabolic substrates that are required for continued function
patient. The impetus for multimodal monitoring of brain func- and survival and to remove toxic byproducts. Even transient
tion arises from both its importance and vulnerability and interruptions in CBF, whether local or global, can injure or kill
also the difficulty in obtaining a satisfactory assessment of func- neural cells. These perturbations may not result in immediate
tion in the setting of numerous insults and processes including cell death, but can initiate metabolic or cellular processes (e.g.,
toxic and metabolic encephalopathy, sedation and chemical re- gene transcription, secondary injury) that may lead to cell death
straints, and primary central nervous system (CNS) processes days, months, or years after the insult. Therefore, clinical moni-
like stroke and traumatic brain injury. toring of neuronal well-being should emphasize early detection
There has been rapid growth and there continues to be and reversal of potentially harmful conditions. Although there
much interest in the field as numerous devices and modali- is limited conclusive data to demonstrate that morbidity and
ties are developed to monitor brain function and processes mortality are reduced by the information gathered from cur-
including intracranial pressure (ICP) monitoring, electroen- rent neurologic monitoring techniques, most clinicians caring
cephalography, and corticography, global and regional brain for patients with critical neurologic illness have confidence that
tissue oxygen monitoring, cerebral blood flow measurements, their use improves management. In this chapter, we review cur-
and neurochemical and cellular metabolism assessment with rently available techniques with emphasis on the current scien-
microdialysis. tific literature and indications for utilization.
As with any diagnostic or therapeutic tool, an understand-
ing of the indications, limitations, risks and benefits of an
intervention are essential in the effective utilization, interpreta-
tion, and application of the obtained information to the man-
agement of the individual patient. Important characteristics of GOALS OF BRAIN
monitoring devices include the ability to detect important ab- MONITORING
normalities (sensitivity), to differentiate between dissimilar dis-
ease states (specificity), and to prompt changes in care that Monitoring devices cannot independently improve outcome.
alter long-term prognosis (Table 28.1). Limitations of tech- Instead, they contribute physiologic data that can be integrated
niques include risks to patients (during placement, use, and into a care plan that, while frequently adding risks (associated
removal), variability errors in generation of data (e.g., calibra- with placement, use, and removal), may lead to an overall de-
tion and drift), and inherent trade-offs between specificity and crease in morbidity and mortality.
sensitivity. Monitors with high specificityvalues fall outside Neurologic monitoring can be categorized into three main
of threshold levels only when a disease state is unequivocally groups: (i) Monitors of neurologic function (e.g., neurologic
presentare unlikely to detect less profound levels of disease, examination, EEG, evoked potentials, functional MRI), (ii)
while monitors with high sensitivity (will detect any value out- Monitors of physiologic parameters (e.g., ICP, cerebral blood
side of the normal range) are likely to demonstrate small devia- flow, transcranial Doppler), and (iii) Monitors of cellular
tions from normal, which may be trivial in individual patients. metabolism (e.g., SjvO2 , NIRS, Brain tissue oxygen tension,
The advantage of multimodal monitoring is it increases the Microdialysis, PET, MRSPECT). Most categorizations are ar-
sensitivity and accuracy of our detection of physiologic and bitrary and obviously overlaps and inter-relationships between
cellular changes that signal further impending clinical deteri- modalities (e.g., blood flow and electrical activity, oxygena-
oration by using different monitoring modalities in a comple- tion, and perfusion) blur the lines of distinction. All cate-
mentary fashion. A legitimate concern raised by some is that gories provide information that may be useful in assessing
the vastly larger amounts of data generated by these devices the current status of the brain and nervous system and in
requires computer-supported data analyses which is costly and directing therapies as well as monitoring responses to inter-
time-consuming and may overwhelm the ill-prepared clinician ventions, but it cannot be overemphasized that the data ob-
and detract whatever benefits may be gained from the new tained from these monitoring devices should always be inter-
technology [1]. Most agree that careful consideration should preted in relation to the overall clinical picture of the individual
go into selecting the appropriate patient to monitor, the modali- patient.
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Chapter 28: Neurologic Multimodal Monitoring 259

TA B L E 2 8 . 1
GLOSSARY OF NEUROLOGIC MONITOR CHARACTERISTICS

Term Definition

Bias Average difference (positive or negative) between monitored values and gold standard values
Precision Standard deviation of the differences (bias) between measurements
Sensitivity Probability that the monitor will demonstrate cerebral ischemia when cerebral ischemia is present
Positive predictive value Probability that cerebral ischemia is present when the monitor suggests cerebral ischemia
Specificity Probability that the monitor will not demonstrate cerebral ischemia when cerebral ischemia is not present
Negative predictive value Probability that cerebral ischemia is not present when the monitor reflects no cerebral ischemia
Threshold value The value used to separate acceptable (i.e., no ischemia present) from unacceptable (i.e., ischemia present)
Speed The time elapsed from the onset of actual ischemia or the risk of ischemia until the monitor provides
evidence

with microvascular changes. Endonucleases which alter gene


CEREBRAL ISCHEMIA regulation and protein synthesis and activate the caspase path-
ways that trigger apoptosis are also released [4,5]. Other pro-
Given the brains dependence and sensitivity to perturbations teins synthesized in response to altered oxygen delivery, such as
in oxygenation many if not all monitors are concerned with hypoxia inducible factors (HIF), have been identified as adap-
the detection of cerebral ischemia defined as cerebral delivery tive mechanisms that respond to variations in oxygen partial
of oxygen (CDO2 ) insufficient to meet metabolic needs. Cere- pressure [6] and may be protective. These multiple pathways
bral ischemia is traditionally characterized as global or focal, and cellular mediators and their interactions are potential areas
and complete or incomplete (Table 28.2). Systemic monitors for therapeutic intervention. Byproducts of these reactions pro-
readily detect most global cerebral insults, such as hypoten- vide potential biomarkers for secondary injury that can be used
sion, hypoxemia, or cardiac arrest. Brain-specific monitors can for monitoring. Our current understanding of the utility of this
provide additional information primarily in situations, such as data is still evolving and currently when a cerebral monitor de-
stroke, SAH with vasospasm, and TBI, in which systemic oxy- tects ischemia, the results must be carefully interpreted. Often,
genation and perfusion appear to be adequate but focal cerebral all that is known is that cerebral oxygenation in the region of
oxygenation may be impaired. the brain that is assessed by that monitor has fallen below a
The severity of ischemic brain damage has traditionally been critical threshold. Such information neither definitively implies
thought to be proportional to the magnitude and duration of
reduced CDO2 . For monitoring to influence long-term patient
morbidity and mortality, prompt recognition of reversible cere-
bral hypoxia/ischemia is essential. Numerous animal studies 30
and human studies using different imaging techniques such as
PET, MRI, and SPECT have concluded that the ischemic thresh-
old for reversible injury or penumbra is a cerebral blood flow
of 20 mL per 100 g per minute below which tissue is at risk
for irreversible damage [2,3]. The tolerable duration of more Paralysis
profound ischemia is inversely proportional to the severity of
(cc / 100 g / min)

20
CBF reduction (Fig. 28.1). Ischemia and hypoxemia initiate a
Local CBF

cascade of cellular reactions that involve multiple pathways in-


cluding energy failure from anaerobic glycolysis with accumu-
lation of lactic acid and increase in lactate/pyruvate ratios, loss
of ion homeostasis and failure of ATP-dependent ion pumps to
maintain ion gradients. This leads to sodium and calcium influx Infarction
10
into the cell and activation of enzymes such as phospholipases
that result in further membrane and cytoskeletal damage, gluta-
mate release and excitotoxicity, lipoperoxidases and free fatty
acid breakdown, and free-radical formation and inflammation

0
TA B L E 2 8 . 2 1 2 3 PERMANENT

CHARACTERISTICS OF TYPES OF CEREBRAL


Time
ISCHEMIC INSULTS (h of MCA occlusion)
FIGURE 28.1. Schematic representation of ischemic thresholds in
Characteristics Examples
awake monkeys. The threshold for reversible paralysis occurs at local
cerebral blood flow (local CBF) of approximately 23 mL/100 m/min.
Global, incomplete Hypotension, hypoxemia, Irreversible injury (infarction) is a function of the magnitude of blood
cardiopulmonary resuscitation flow reduction and the duration of that reduction. Relatively severe
Global, complete Cardiac arrest ischemia is potentially reversible if the duration is sufficiently short.
Focal, incomplete Stroke, subarachnoid hemorrhage with (From Jones TH, Morawetz RB, Crowell RM, et al: Thresholds of
vasospasm focal cerebral ischemia in awake monkeys. J Neurosurg 54:773782,
1981, with permission.)
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260 Section II: Minimally Invasive Monitoring

100 100 100


(mL/100 g/min)

75 75
CBF

50 50 50

25 25

0 0 0
1 2 3 4 5 6 50 130 20 40 60 80
CMRO2 MAP PaCO2
A (mL/100 g/min) B (mm Hg) C (mm Hg)

FIGURE 28.2. A: The normal relationship between the cerebral metabolic rate of oxygen consumption
(CMRO2 ) and cerebral blood flow (CBF) is characterized by closely couple changes in both variables.
Normally, CBF is 50 mL per 100 g per minute in adults (open triangle). As CMRO2 increases of decreases,
CBF changes in a parallel fashion (solid line). B: Effect of mean arterial pressure (MAP) on CBF. Note
that changes in MAP produce little change in CBF over a broad range of pressures. If intracranial pressure
(ICP) exceeds normal limits, substitute cerebral perfusion pressure on the horizontal axis. C: Effect of
PaCO2 on CBF. Changes in PaCO2 exert powerful effects on cerebral vascular resistance across the entire
clinically applicable range of values.

that ischemia will necessarily progress to infarction nor does and SjvO2 [9,10]. For this reason, hyperventilation has fallen
it clearly define what biochemical or genetic transcriptional out of favor as a treatment modality for intracranial hyper-
changes may subsequently occur. Also, because more severe tension. If hyperventilation is required to acutely reduce ICP
ischemia produces neurologic injury more quickly than less se- to bridge a patient to emergent surgery for example, admin-
vere ischemia, time and dose effects must be considered. More istration of an increased inspired oxygen concentration can
important, if regional ischemia involves structures that are not markedly increase SjvO2 (Fig. 28.3). In response to decreasing
components of the monitored variable, then infarction could arterial oxygen content (CaO2 ), whether the reduction is sec-
develop without warning. ondary to a decrease of hemoglobin (Hgb) concentration or
In healthy persons, CBF is tightly regulated through multi- of arterial oxygen saturation (SaO2 ), CBF normally increases,
ple pathways such that CDO2 is adjusted to meet the metabolic although injured brain tissue has impaired ability to increase
requirements of the brain. In the normal, coupled relation- CBF [11].
ship, CBF is dependent on the cerebral metabolic rate for oxy-
gen (CMRO2 ), which varies directly with body temperature
and with the level of brain activation (Fig. 28.2A). As CMRO2
increases or decreases, CBF increases or decreases to match TECHNIQUES OF NEUROLOGIC
oxygen requirements with oxygen delivery. Pressure autoregu-
lation maintains CBF at a constant rate (assuming unchanged
MONITORING
metabolic needs) over a wide range of systemic blood pressures
(Fig. 28.2B). If pressure autoregulation is intact, changes of Neurologic Examination
cerebral perfusion pressure (CPP) do not alter CBF over a range
of pressures of 50 to 130 mm Hg. CPP can be described by the Frequent and accurately recorded neurologic examinations are
equation CPP = MAP ICP, where MAP equals mean arterial an essential aspect of medical care, but are often limited in pa-
pressure. After neurologic insults (e.g., TBI), autoregulation of tients with moderate-to-severe neurologic compromise. Neu-
the cerebral vasculature may be impaired such that CBF may rologic examination quantifies three key characteristics: level
not increase sufficiently in response to decreasing CPP [7]. This of consciousness, focal brain dysfunction, and trends in neuro-
failure to maintain adequate CDO2 can lead to ischemia and logic function. Recognition of changing consciousness or new
add to preexisting brain injury, a process termed secondary in- focal deficits may warn of a variety of treatable conditions, such
jury, at blood pressures that would not normally be associated as progression of intracranial hypertension, new mass lesions
with cerebral ischemia/injury. Normally, arterial partial pres- such as expansion of intraparenchymal contusions or subdural
sure of carbon dioxide, (PaCO2 ) significantly regulates cerebral hematoma and systemic complications of intracranial pathol-
vascular resistance over a range of PaCO2 of 20 to 80 mm Hg ogy, such as hyponatremia.
(Fig. 28.2C). CBF is acutely halved if PaCO2 is halved, and The GCS score, originally developed as a tool for the as-
doubled if PaCO2 is doubled. This reduction in CBF (via arte- sessment of impaired consciousness [12], has also been used as
riolar vasoconstriction) results in a decrease in cerebral blood a prognostic tool for patients with TBI [13]. The GCS score
volume and a decrease in ICP. Conceptually, decreasing PaCO2 at the time of initial hospitalization is used to characterize the
to decrease ICP may appear to be desirable. Hyperventilation severity of TBI, with severe TBI defined as a GCS score less than
as a clinical tool was described by Lundberg et al. [8] in 1959 as or equal to 8, moderate TBI as a GCS score of 9 to 12, and mild
a treatment for increased ICP and was a mainstay of treatment TBI as that associated with a GCS score greater than 12. Lower
for over 40 years. However, in healthy brain, there are limits to GCS scores are generally associated with poorer long-term out-
maximal cerebral vasoconstriction with falling PaCO2 (as well comes, although correlation to individual patients with TBI is
as vasodilation with increasing PaCO2 ), such that, as CBF de- difficult because of the significant variations in mortality rates
creases to the point of producing inadequate CDO2 , local va- and functional outcome [14]. Significant concern has arisen re-
sodilatory mechanisms tend to restore CBF and CDO2 . As a garding the validity of the initial GCS score on presentation
consequence, in healthy brain, hyperventilation does not pro- given the aggressive prehospital management of these patients
duce severe cerebral ischemia; however, after TBI, hypocapnia over the last decade or so, that includes sedation and intubation
can generate cerebral ischemia as reflected in decreased PbtO2 in the field or the administration of paralytics and sedatives in
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Chapter 28: Neurologic Multimodal Monitoring 261

80

75

70
SjvO2 %

65

FIGURE 28.3. The effect of hyperoxia


60 on percentage of oxygen saturation of
jugular venous blood (SjvO2 ) at two
levels of PaCO2 . p < 0.001 for SjvO2
at PaCO2 2530 mm Hg at each PaO2 .
55 PaO2 100150 mm Hg p < 0.001 for SjvO between PaO at
2 2
each PaCO2 level. (From Thiagarajan
PaO2 200250 mm Hg A, Goverdhan PD, Chari P, et al: The ef-
fect of hyperventilation and hyperoxia
50
on cerebral venous oxygen saturation
30 mm Hg 25 mm Hg 30 mm Hg in patients with traumatic brain injury.
PaCO2 Anesth Analg 87:850853, 1998, with
permission.)

the emergency room. Some authors have reported a loss of pre- in healthy individuals. After brain injury, autoregulation may
dictive value of the GCS score from 1997 onwards and call for a become impaired, especially in traumatically brain-injured pa-
critical reconsideration of its use [15]. Other studies done have tients. Chesnut et al. [17,18] reported that even brief periods
looked at GCS in the field versus GCS upon arrival and have of hypotension (systolic blood pressure less than 90 mm Hg)
found good correlation and prognostic value in predicting out- worsened outcome after TBI, and recommended that systolic
come and have even found the changes in scores from field GCS blood pressure be maintained greater than 90 mm Hg (with
to arrival GCS to be highly predictive of outcome in patients possible benefit from higher pressures). These recommenda-
with moderate to severe TBI [16]. Many centers use the best tions have also been promoted by the Brain Trauma Foundation
GCS or postresuscitation GCS in the first 24 hours or just the for patients with severe TBI [19]. To achieve this goal, the use
motor component of the GCS instead of initial GCS given these of vasoactive substances, such as norepinephrine, may be re-
issues. Nevertheless, the GCS score is popular as a quick, re- quired [20]. Nevertheless, optimal blood pressure management
producible estimate of level of consciousness (Table 28.3), has
become a common tool for the serial monitoring of conscious-
ness, and has been incorporated into various outcome models,
such as the Trauma score, APACHE II, and the Trauma-Injury TA B L E 2 8 . 3
Severity score. The GCS score, which includes eye opening,
motor responses in the best functioning limb, and verbal re- GLASGOW COMA SCALE
sponses is limited and by no means replaces a thoughtful and
focused neurologic examination. It should be supplemented by Component Response Score
recording pupillary size and reactivity, cranial nerve examina-
Eye opening Spontaneously 4
tion and more detailed neurologic testing depending on the rel-
To verbal command 3
evant neuroanatomy involved in the disease process. Even so,
To pain 2
the use of serial GCS determinations remains a common tool
None 1
in the management of patients with neurologic dysfunction.
Subtotal: 14
Motor response Obeys verbal command 6
(best extremity) Localizes pain 5
Systemic Monitoring Flexion-withdrawal 4
Although not specific to neurologic monitoring, systemic pa- Flexor (decorticate 3
rameters, including blood pressure, arterial oxygen saturation posturing)
(SaO2 ), PaCO2 , serum glucose concentration, and temperature, Extensor (decerebrate 2
have clinical relevance in the management of patients with neu- posturing)
rologic dysfunction or injury. The relationships between these No response (flaccid) 1
systemic variables and long-term outcome after neurologic in- Subtotal: 16
sults are closely linked and are subject to continuing research. Best verbal Oriented and converses 5
Perhaps the most important systemic monitor is blood pres- response Disoriented and converses 4
sure, as CBF is dependent on the relationship between CPP Inappropriate words 3
and cerebral vascular resistance (CVR), and can be modeled Incomprehensive sounds 2
generally by the equation: CBF = CPP/CVR. As previously dis- No verbal response 1
cussed, CBF is maintained relatively constant over a wide range Subtotal: 15
of blood pressures (pressure autoregulation) through arteriolar Total: 315
changes in resistance (assuming no change in brain metabolism)
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262 Section II: Minimally Invasive Monitoring

for patients with TBI has yet to be defined. Some clinical data to both diagnosis and length of stay [43,44]. Hyperthermia
suggest that the influence of hypotension on outcome after TBI is generally associated with poorer outcome when associated
is equivalent to the influence of hypotension on outcome after with neurologic injury in adults and children [45], but a causal
non-neurologic trauma [21]. Proposed treatment protocols in- link with adverse outcome (as with serum glucose levels) is
clude CPP greater than 70 mm Hg [22], greater than 60 mm lacking. It is unclear whether increased temperatures result in
Hg [23], or greater than 50 mm Hg [24]. The augmentation of worsened long-term neurologic outcome, or whether a greater
CPP above 70 mm Hg with fluids and vasopressors has, how- severity of brain injury is associated with more frequent or se-
ever, been associated with increased risk of acute respiratory vere increases in systemic temperature.
distress syndrome and is not universally recommended [23]. The method of temperature monitoring is important. Ther-
Another essential step in insuring adequate CDO2 is the mal gradients exist throughout the body, and the site of mea-
maintenance of adequate CaO2 , which in turn is dependent surement influences the diagnosis of hypothermia, normother-
on Hgb and SaO2 ; therefore, anemia and hypoxemia can re- mia, or hyperthermia. Measurements of systemic temperature
duce CDO2 , which would normally result in compensatory in- may underestimate brain temperature. In studies of tempera-
creases in CBF. However, these compensatory mechanisms are ture monitoring by site, variations of up to 3 C have been iden-
limited. As SaO2 (or PaO2 ) decreases below the compensatory tified between the brain and other routinely used monitoring
threshold, SjvO2 and jugular venous oxygen content (CjvO2 ), sites, emphasizing the importance of monitoring site selection
which reflect the ability of CDO2 to supply CMRO2 , also de- in patients with neurologic injury and the need to appreciate
crease. The correlation is most evident below a PaO2 of ap- the difference between brain temperature and the active site of
proximately 60 mm Hg, the PaO2 at which SaO2 is 90% and measurement used clinically for a given patient.
below which SaO2 rapidly decreases. In contrast, as Hgb is
reduced by normovolemic hemodilution, SjvO2 remains rela-
tively constant unless severe anemia is produced [25]. EEG/Electrocorticography
The management of arterial CO2 in patients with neurologic
injury has changed dramatically in the past 10 years. Although Electroencephalographic (EEG) monitoring has long been used
hyperventilation as a management strategy for increased ICP in neurology for diagnosis and intraoperative monitoring, but
was routine in the 1990s, it is now reserved for acute or life- has less frequently been used as a neurologic monitoring tech-
threatening increases in the intensive care unit (ICU) and is no nique in critically ill patients. EEG is indicated in response to
longer recommended for routine use. Having been associated suspicion of a new or progressive abnormality such as cerebral
with cerebral ischemia in children and adults [9,10] with se- ischemia or new onset of seizures. The cortical EEG or elec-
vere TBI, hyperventilation is least likely to be harmful when trocorticography, which is altered by mild cerebral ischemia
combined with monitoring, such as SjvO2 or PbtO2 , that can and abolished by profound cerebral ischemia, can be used to
identify cerebral ischemia. indicate potentially damaging cerebral hypoperfusion. More
Hyperglycemia increased injury in experimental TBI [26] recent research has documented its utility in the detection of
and was associated with worse outcome in clinical TBI [27,28], cortical spreading depression and peri-infarct depolarizations
although it is difficult to distinguish between elevated glucose (proposed to be early indicators of delayed ischemic injury) in
causing worsened outcome versus increased severity of TBI in- the acutely injured human cortex in traumatic brain injury and
ducing more elevated glucose levels [29]. In critically ill patients subarachnoid hemorrhage [46,47]. The EEG can document
requiring mechanical ventilation, elevated glucose levels were seizures, either convulsive or nonconvulsive, and provide infor-
associated with worsened outcomes [30], and current recom- mation as to the efficacy of antiseizure therapy. Other functions
mendations are to tightly control serum glucose in critically ill include defining the depth or type of coma, documenting focal
patients in the medical and surgical ICU [31]. Caution must be or lateralizing intracranial abnormalities, and the diagnosis of
exercised in the brain injured patient as there is also evidence brain death.
to suggest that hypoglycemia can be more detrimental than hy- If the EEG is to be used for monitoring, care must be taken
perglycemia and microdialysis studies in traumatic brain injury and weaknesses of the technique appreciated [48]. In the ICU,
patients found that extracellular glucose concentration is low electrical noise from other equipment may produce artifacts
after TBI and is associated with markers for tissue distress and and interfere with technically adequate tracings. Continuous
poor outcome [32]. EEG recording was cumbersome in the past owing to the sheer
The monitoring and management of body temperature re- volume of data (300 pages per hour of hard copy on as many as
mains an important aspect of care for critically ill patients. Hy- 16 channels), but techniques for digital recording and network-
pothermia and hyperthermia should be considered separately ing direct computer recording of EEG data are now available
in this context. The use of hypothermia as a treatment for brain given adequate computer power and storage. Scalp fixation has
injury, while demonstrating benefit in animals [33] and in some also been a significant limiting factor, although newer fixation
phase II human studies, has not shown consistent benefit in techniques are easier to apply and more stable. Techniques of
larger studies [34] and is not recommended for general use mathematical data analysis, such as rapid Fourier analysis, can
in TBI [35,36]. Although the largest clinical trials (NABISH- be used to determine the relative amplitude in each frequency
1 and Hypothermia Pediatric Head Injury Trial Investigators band (deltaless than 4 Hz, theta4 to 8 Hz, alpha8 to
and the Canadian Critical Care Trials Group) were negative 13 Hz, betagreater than 13 Hz), which can then be displayed
[37,38], there were numerous smaller human trials and meta- graphically in formats such as the compressed spectral array
analyses that suggested improved neurologic outcomes with or density spectral array. Alpha variability has been found to
hypothermia in TBI. Some authors suggest that the failure of predict vasospasm/delayed cerebral ischemia in subarachnoid
these trials was because of poor protocol design and lack of hemorrhage patients [49] and the percentage of alpha variabil-
proper management of the side effects of hypothermia [39,40]. ity was found to have prognostic value in traumatic brain injury
In contrast, induced hypothermia after resuscitation from car- [50]. Analytic software has been developed that processes the
diac arrest (secondary to ventricular tachycardia or fibrillation) raw EEG signal to provide single number interpretation of the
has improved outcome in some trials [41,42]. Research into depth of sedation. These devices have been recommended
this complex area is ongoing, and clinical practice is likely to for use during general anesthesia as a means to reduce the risk
undergo further refinement. of awareness [51], although the scientific justification for this
Hyperthermia is common in critically ill patients, occur- claim is not conclusive. The American Society of Anesthesiolo-
ring in up to 90% of patients with neurologic disease, related gists has developed a practice advisory on this issue [52]. Use of
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Chapter 28: Neurologic Multimodal Monitoring 263

this type of monitoring has also been implemented by some for motor tracts. Stimulation of proximal motor tracts (cortical or
use in the ICU for monitoring sedation levels in the critically ill, spinal) and evaluation of subsequent responses yield informa-
the utility of which has yet to be proven [53,54]. All devices use tion that can be used for intraoperative and early postoperative
proprietary analysis of an EEG signal (either spontaneous or neurosurgical management. Induction of motor EP and its in-
evoked, with or without electromyogram monitoring), which terpretation is exquisitely sensitive to sedative, analgesic, and
is converted to a single number that is intended to correspond anesthetic drugs, making clinical use difficult when drugs are
to an awareness level based on an arbitrary scale. The future given concurrently. Despite these limitations, motor EP evalu-
role and evidence of improved patient outcomes with this mon- ation has been successfully used for the management of neuro-
itoring modality remain unclear. A more detailed discussion of ICU patients and may become more common as techniques and
the clinical indications, technical aspects, and limitations can equipment improve [56,57].
be found in a recent review [55]. The sensitivity of EP monitoring is similar to that of EEG
monitoring. EPs, especially brainstem auditory EPs, are rela-
tively robust, although they can be modified by trauma, hy-
EVOKED POTENTIALS poxia, or ischemia. Because obliteration of EPs occurs only
under conditions of profound cerebral ischemia or mechanical
Sensory-evoked potentials (EPs), which include somato- trauma, EP monitoring is one of the most specific ways in which
sensory-evoked potentials (SSEPs), brainstem auditory EPs, to assess neurologic integrity in specific monitored pathways.
and visual EPs, can be used as qualitative threshold monitors However, as with the discussion of cerebral ischemia, there is
to detect severe neural ischemia. Unlike EEG that records the a dosetime interaction that ultimately determines the magni-
continuous, spontaneous activity of the brain, EPs evaluate the tude of cerebral injury. As a result, neurologic deficits occur
responses of the brain to specific stimuli. To record SSEPs, that have not been predicted by changes in EPs, and severe
stimuli are applied to a peripheral nerve, usually the median changes in EPs may not be followed by neurologic deficits. The
nerve at the wrist or posterior tibial nerve at the ankle, by a most definitive indication for SSEPs is in the prognostication
low-amplitude current of approximately 20 milliseconds in du- of anoxic brain injury from cardiac arrest. The absence of the
ration. The resultant sensory (afferent) nerve stimulation and N20 response on bilateral SSEPs of the median nerve within
resultant cortical response to the stimulus are recorded at the 3 days postarrest has been found to be a reliable predictor
scalp. Repeated identical stimuli are applied and signal aver- of negative outcome or recovery of consciousness in anoxic
aging is used to remove the highly variable background EEG postarrest coma and is part of the AAN practice parameter in
and other environmental electrical noise and thereby visualize the prognostication of postanoxic coma [58].
reproducible evoked responses (Fig. 28.4).
EPs are described in terms of the amplitude of cortical re-
sponse peaks and the conduction delay (latency) between the
stimulus and the appearance of response waveform. Because INTRACRANIAL PRESSURE
peripheral nerve stimulation can be uncomfortable, SSEPs are MONITORING
usually obtained from sedated or anesthetized patients. SSEPs
are unaffected by neuromuscular blocking agents but may be The symptoms and signs of intracranial hypertension are
significantly influenced by sedative, analgesic, and anesthetic neither sensitive nor specific. Usually, the physical findings
agents, often in a dose-dependent manner. In general, however, associated with increasing ICP (e.g., Cushings response
the doses of drugs required to influence EPs are sufficient to hypertension and Cushings triadhypertension, reflex brady-
produce general anesthesia and are not usually clinically im- cardia, and alterations in respiratory function) become
portant in the ICU. If a patient is undergoing EP monitoring apparent only when intracranial hypertension has become suf-
and requires large doses of analgesic or sedative agents, po- ficiently severe to injure the brain. Likewise, papilledema is
tential impairment of monitoring should be considered. Motor a late development and is often difficult to identify clinically.
EPs represent a method of selectively evaluating descending Because ICP cannot otherwise be adequately assessed, direct

1
TRIAL 1V

100 msec
FIGURE 28.4. Averaging reduces
10
background noise. After 100 trials,
TRIAL 1V this visual evoked potential (EP) is
relatively noise-free. The same EP
is hard to distinguish after only 10
trials and would be impossible to
find in the original unaveraged data.
100
(From Nuwer MR: Evoked Potential
TRIAL 1V
Monitoring in the Operating Room.
New York, Raven Press, 1986, p 29,
with permission.)
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264 Section II: Minimally Invasive Monitoring

measurement and monitoring of ICP has become a common but fixation and equipment reliability are practical issues. This
intervention, especially in the management of TBI [59], and technique is used uncommonly for these reasons.
less commonly after critical illnesses such as SAH or stroke. Intraparenchymal placement of a fiber-optic catheter is also
Although there is no class 1 evidence that the use of this tech- possible and is associated with complications similar to ventric-
nique improves outcomes, there is a large body of clinical ev- ular fiber-optic catheters. Complications are generally noted to
idence supporting its use to guide therapeutic interventions in be highest with ventriculostomies (when compared with fiber-
traumatic brain injury that have potential risks (such as ag- optic catheter usage), and complications of ICP monitoring are
gressive osmotherapy, induced hypothermia and barbiturate associated with a worse GCS score.
coma), to aid in the detection intracranial mass lesions and to Management decisions based on ICP data are the focus
provide prognostic data [60]. ICP monitoring has been found of ongoing debate and study. Clinical studies after TBI have
to improve outcome prediction in TBI and next to clinical pa- demonstrated that increased ICP is associated with worsened
rameters such as age, GCS motor score and abnormal pupillary outcome [68]. Therefore, control of ICP has been considered
responses, the proportion of hourly ICP recordings greater than by some clinicians to be the primary focus of treatment [24],
20 mm Hg was the next most significant predictor of outcome while other clinicians have considered restoration of CPP (by
in an analysis done of the National Traumatic Coma Data Bank increasing MAP) to be the primary goal of medical manage-
[61]. Despite this, the debate continues on how to use ICP data ment [21]. To date, the ideal approach has not been established
to change patient care and reduce morbidity and mortality. It is by outcome trials; therefore, practice patterns remain variable
unlikely that a large randomized clinical trial will ever be done [69]. Clinical experience with ICP monitoring of head-injured
given the lack of clinical equipoise. The Brain Trauma Founda- patients has resulted in publication of clinical guidelines using
tion/American Association of Neurosurgeons Guidelines rec- an evidence-based approach (Fig. 28.5) [70].
ommend ICP monitoring in all patients with severe TBI (GCS
<8) and an abnormal CT scan or a normal scan with patients
who are greater than 40 years old, have motor posturing, or
a systolic BP <90 mm Hg [62,63]. Because pressure gradients CEREBRAL BLOOD FLOW
may exist among various sites within the calvarium, it may MONITORING
be advantageous to monitor in or adjacent to the most severely
damaged hemisphere [64], some even recommend bilateral ICP The first quantitative clinical method of measurement of CBF,
monitoring to circumvent this problem [65]. the KetySchmidt technique, calculated global CBF from the
ICP functions as the outflow pressure apposing MAP difference between the arterial and jugular bulb concentration
(CPP = MAP ICP) when ICP exceeds jugular venous pres- curves of an inhaled, inert gas as it equilibrated with blood and
sure. Because the skull is not distensible, the brain, cere- brain tissue. Later techniques used extracranial gamma detec-
brospinal fluid (CSF), and cerebral blood volume have little tors to measure regional cortical CBF from washout curves af-
room to expand without increasing ICP. It is important to ap- ter intracarotid injection of a radioisotope such as 133-xenon
preciate that some increase in intracranial volume is possible (Xe 133). Carotid puncture was avoided by techniques that
without much change in ICP, but when the compensatory mech- measured cortical CBF after inhaled or intravenous adminis-
anisms are exhausted, even small changes in volume can lead tration of Xe 133, using gamma counting of exhaled gas to
to significant increases in pressure. Although CBF cannot be correct clearance curves for recirculation of Xe 133. Because Xe
directly inferred from knowledge of MAP and ICP, severe in- is radiodense, saturation of brain tissue increases radiographic
creases in ICP reduce CPP and CBF. ICP monitoring provides density in proportion to CBF. Imaging of the brain after equi-
temporally relevant, quantitative information. The problems libration with stable (nonradioactive) Xe provides a regional
associated with ICP monitoring fall generally into three cat- estimate of CBF that includes deep brain structures. Clinical
egories: direct morbidity due to monitor placement (e.g., in- studies of CBF after TBI performed using stable xenon com-
tracranial hemorrhage, cortical damage, and infection), inac- puted tomography (CT) have prompted a radical revision of
curate measurement, and misinterpretation or inappropriate conventional understanding by demonstrating that one third
use of the data. Clinically, one of three sites is used to mea- of patients had evidence of cerebral ischemia within 8 hours
sure ICP: a lateral ventricle, the brain parenchyma, and much of trauma. Although slow in becoming a routine clinical tool,
less commonly the subdural space. Ventricular catheterization, Xe CT is becoming a more common technique for monitor-
when performed using strict asepsis, is the method of choice for ing CBF in patients. The use of helical and spiral CT scanners
ICP monitoring and CSF drainage [66] in patients with acute (with very short acquisition times) reduces the radiation expo-
intracranial hypertension and excess CSF (i.e., acute hydro- sure to the patient and decreases the time needed for a scan,
cephalus). In practice, intraventricular catheters may be diffi- improving clinical utility [71]. A newer method of measuring
cult to place if cerebral edema or brain swelling has compressed CBF that provides continuous bedside quantitative measure-
the ventricular system. Intraventricular pressure monitoring ments is the thermal diffusion technique. This consists of the
can also be performed with fiber-optic catheters (instead of a insertion of a microprobe into the brain parenchyma with a
hollow catheter) that use a variable reflectance pressure sensing thermistor at the tip and a temperature sensor proximal to it.
system (transducer tip) to measure pressure (Camino Laborato- The thermistor is heated to 2 degrees above tissue temperature
ries, San Diego, CA). These fiber-optic catheters are less suscep- and CBF is calculated using the thermal gradient and provides
tible to short-term malfunction than conventional, fluid-filled a quantified regional CBF measurement in mL per 100 g per
catheters but may slowly and unpredictably drift over days to minute. Some studies suggest a correlation with regional brain
weeks [67]. tissue oxygenation and possible role in guiding management
Pressure monitoring from the subdural space may use a of ICP. Technical issues such as the invasive nature of the de-
fluid-coupled bolt (simple transcranial conduit), fluid-coupled vice, frequent calibration, and the limitations seen in the febrile
subdural catheters (or reservoirs), or fiber-optic transducer- patient have kept this method from becoming more widely
tipped catheters (see earlier). Because subdural bolts are open adopted [72]. Another CT-based technique, perfusion CT, uses
tubes facing end-on against the brain surface, brain tissue may iodinated contrast infusion with repeated images to calculate
herniate into the system, obstructing the system, distorting local CBF. This technique is limited to smaller regions and
measurements, and potentially damaging the cerebral cortex. may not provide uniform results between brain regions [73].
Reservoir systems require surgical placement into the subdural Other techniques, such as single-photon emission CT (SPECT)
space. Fiber-optic systems do not have these specific problems, and magnetic resonance perfusion imaging also can provide
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Chapter 28: Neurologic Multimodal Monitoring 265

GCS 8 Surgery as indicated

Yes
Insert ICP monitor

Maintain CPP
(age appropriate)

Yes NO
ICP?

Yes

Sedation and analgesia


HOB @ 30

Yes No
ICP?

Yes

Drain CSF if
ventriculostomy present

Consider Carefully
Yes No withdraw
repeating ICP?
CT scan ICP
Yes treatment

Neuromuscular blockade

Yes No
ICP?

Yes

Hyperosmolar therapy
Mannitol PRN
(3% saline infusion)

May repeat if serum May continue if serum


osm <320 osm <360
Yes No
ICP?

Yes
Mild hyperventilation
(PaCO2 30 - 35 mm Hg)

Yes No
ICP?

Yes

Second tier therapy

FIGURE 28.5. Critical pathway for treatment of intracranial hypertension in the pediatric patient with
severe head injury. ICP, intracranial pressure. (From Adelson PD, Bratton SL, Carney NA, et al: Critical
pathway for the treatment of established intracranial hypertension in pediatric traumatic brain injury. Ped
Crit Care Med 4(3)[Suppl]:S65S67, 2003, with permission.)
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266 Section II: Minimally Invasive Monitoring

200 is distributed to the right and left lateral sinus contribute to dif-
ferences between the two jugular bulbs. Ideally, a jugular bulb
Flow Velocity cm/sec

catheter should be placed on the dominant side, which can be


150
identified as the jugular vein that, if compressed, produces the
greater increase in ICP or as the vein on the side of the larger
100 jugular foramen as detected by CT [76].
In general SjvO2 reflects the adequacy of CDO2 to support
CMRO2 , but mixed cerebral venous blood, like mixed systemic
50 blood, represents a global average of cerebral venous blood
from regions that are variably perfused and may not reflect
0 marked regional hypoperfusion/ischemia of small regions. In
0 7 14 21 28 contrast to ICP and CPP, which provide only indirect informa-
tion concerning the adequacy of CDO2 to support CMRO2 ,
Days After SAH SjvO2 directly reflects the balance between these variables on a
FIGURE 28.6. Mean flow velocity (FV, in cm/sec) curves of 18 patients global or hemispheric level. CBF, CMRO2 , CaO2 , and CjvO2
with laterally localized aneurysms (arising from the internal carotid and are modeled by the equation: CMRO2 = CBF (CaO2 CjvO2 ).
middle cerebral arteries). The side of the ruptured aneurysm (continu- In healthy brain, if CMRO2 remains constant as CBF decreases,
ous line) shows a higher FV than the unaffected side (dotted line). SAH, SjvO2 and CjvO2 decrease [25]. If flow-metabolism coupling is
subarachnoid hemorrhage. (From Seiler RW, Grolimund P, Aaslid R, intact, decreases in CMRO2 result in parallel decreases in CBF
et al: Cerebral vasospasm evaluated by transcranial ultrasound corre- while SjvO2 and CjvO2 remain constant [25]. Abnormally low
lated with clinical grade and CT-visualized subarachnoid hemorrhage. SjvO2 (i.e., less than 50%, compared to a normal value of 65%)
J Neurosurg 64:594600, 1986, with permission.) suggests the possibility of cerebral ischemia; but normal or el-
evated SjvO2 does not prove the adequacy of cerebral perfu-
sion because of possible saturation averaging between normal
information about CBF, but their clinical utility is still currently and abnormal areas of perfusion. This is especially true for fo-
being studied [71]. Transcranial Doppler ultrasonography cal areas of hypoperfusion. Therefore, the negative predictive
can be used to estimate changes in CBF. In most patients, cere- value of a normal SjvO2 is poor. After placement of a jugular
bral arterial flow velocity can be measured easily in intracranial catheter, monitoring of SjvO2 can be achieved through repeated
vessels, especially the middle cerebral artery, using transcranial blood sampling. However, repeated blood sampling yields only
Doppler ultrasonography. Doppler flow velocity uses the fre- snapshots of cerebral oxygenation and thus provides dis-
quency shift, proportional to velocity, which is observed when continuous data that may miss rapid changes in saturation. To
sound waves are reflected from moving red blood cells. Blood achieve continuous monitoring of SjvO2 , indwelling fiber-optic
moving toward the transducer shifts the transmitted frequency oximetric catheters have been used. Because oxyhemoglobin
to higher frequencies; blood moving away, to lower frequen- and deoxyhemoglobin absorb light differently, SjvO2 can be
cies. Velocity is a function of both blood flow rate and vessel determined from differential absorbance. Oximetric jugular
diameter. If diameter remains constant, changes in velocity are bulb catheters have proven somewhat challenging to maintain,
proportional to changes in CBF; however, intersubject differ- requiring frequent recalibration, repositioning, and confirma-
ences in flow velocity correlate poorly with intersubject differ- tion of measured saturation by analyzing blood samples in
ences in CBF. Entirely noninvasive, transcranial Doppler mea- a cooximeter. The highest frequency of confirmed desatura-
surements can be repeated at frequent intervals or even applied tion episodes occurs in patients with intracerebral hematomas,
continuously. The detection and monitoring of post-SAH va- closely followed by those with SAH. In patients with TBI, the
sospasm remains the most common use of transcranial Doppler number of jugular desaturations is strongly associated with
(Fig. 28.6) [74]. However, further clinical research is necessary poor neurologic outcome; even a single desaturation episode is
to define those situations in which the excellent capacity for associated with a doubling of the mortality rate [77]. Clinical
rapid trend monitoring can be exploited including assessment application of jugular venous bulb cannulation has been lim-
of vascular autoregulation, ancillary testing to detect intracra- ited, perhaps in part because the technique is invasive, although
nial hypertension and brain death. the risks of cannulation injury, including hematoma and injury
to the adjacent carotid, are low. Several modifications of jugu-
lar venous oxygen monitoring have been proposed. Cerebral
extraction of oxygen, which is the difference between SaO2
JUGULAR BULB VENOUS and SjvO2 divided by SaO2 , is less confounded by anemia than
OXYGEN SATURATION the cerebral A-VDO2 [78]. Another concept, termed cerebral
hemodynamic reserve, is defined as the ratio of percentage of
Several measurements of cerebral oxygenation are clinically change in global cerebral extraction of oxygen (reflecting the
useful, including measurement of SjvO2 . To insert a retrograde balance between CMRO2 and CBF) to percentage of change in
jugular venous bulb catheter, the internal jugular vein can be CPP [79]. This equation attempts to integrate cerebral hemo-
located by ultrasound guidance or by external anatomic land- dynamics and metabolism with intracranial compliance. Cruz
marks and use of a seeker needle, namely, the same technique et al. [78] found that cerebral hemodynamic reserve decreased
used for antegrade placement of jugular venous catheters. Once as intracranial compliance decreased, even as a consequence
the vessel is identified, the catheter is directed cephalad, toward of minor elevations in ICP. Theoretically, this variable may al-
the mastoid process, instead of centrally. A lateral cranial ra- low more precise management of cerebral hemodynamics in
diograph can confirm the position just superior to the base of patients with decreased intracranial compliance.
the skull. The decision to place a jugular bulb catheter in the
left or right jugular bulb is important. Simultaneous measure-
ments of SjvO2 in the right and left jugular bulb demonstrate BRAIN TISSUE OXYGEN TENSION
differences in saturation [75], suggesting that one jugular bulb
frequently is dominant, carrying the greater portion of cere- Another promising technique for monitoring the adequacy of
bral venous blood. Differences in the cross-sectional areas of CDO2 is direct assessment of PbtO2 . Monitoring of PbtO2
the vessels that form the torcula and the manner in which blood overcomes one important limitation of SjvO2 monitoring,
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Chapter 28: Neurologic Multimodal Monitoring 267

which is that the global saturation measurements provide no ter clinical trial is in the planning stages but has not started
information about regional or focal tissue oxygenation. Only recruiting patients yet (BOOST-2).
relatively profound focal global ischemia causes SjvO2 to de-
crease to less than the accepted critical threshold of 50%. Even
severe regional ischemia may not result in desaturation if ve- NEUROCHEMICAL MONITORING
nous effluent from other regions is normally saturated, in part
because the absolute flow of poorly saturated blood returning Neuronal injury is associated with the release or production
from ischemic regions is by definition less per volume of tis- of chemical markers such as free radicals, inflammatory me-
sue than flow from well-perfused regions, resulting in a smaller diators, metabolic products, and excitatory amino acids [4].
percentage of poorly oxygenated to well-oxygenated blood. In- Neurochemical monitoring via microdialysis allows assessment
tracranial, intraparenchymal probes have been developed that of the chemical milieu of cerebral extracellular fluid, provides
monitor only PbtO2 or that also monitor brain tissue PCO2 and valuable information about neurochemical processes in vari-
pH [79]. Modified from probes designed for continuous mon- ous neuropathologic states, and is used clinically in the man-
itoring of arterial blood gases, intraparenchymal probes can agement of severe TBI [86] and SAH [87,88]. There is data
be inserted through multiple-lumen ICP monitoring bolts. Al- to suggest that chemical changes detected by microdialysis
though these probes provide no information about remote re- precede secondary neurologic injury and clinical worsening
gions, they nevertheless provide continuous information about in intracranial hypertension, subarachnoid hemorrhage, and
the region that is contiguous to the probe. They also carry the ischemic stroke. Substances monitored via microdialysis in-
theoretical risk of hematoma formation, infection, and direct clude energy-related metabolites such as glucose, lactate, pyru-
parenchymal injury. Evaluation of PbtO2 after severe TBI has vate, adenosine, and xanthine; neurotransmitters such as gluta-
shown that low partial pressures (PbtO2 less than 10 mm Hg mate, aspartate, gamma-amino butyric acid; markers of tissue
for greater than 15 minutes) powerfully predict poor outcomes damage such as glycerol and potassium [89], and alterations in
and that PbtO2 probes are safe [80,81]. Both PbtO2 and SjvO2 membrane phospholipids by oxygen radicals [90]. Lactate lev-
may reflect changes in cerebral oxygenation secondary to alter- els and lactate/pyruvate ratios are reliable markers of ischemia
ations in CBF (Fig. 28.7) [82]. However, comparisons of simul- and have been found to correlate well with PET, cerebral per-
taneous PbtO2 and SjvO2 monitoring suggest that each monitor fusion pressure and jugular venous bulb oxygen saturation val-
detects cerebral ischemia that the other fails to detect. In 58 pa- ues and associated with outcome in traumatic brain injury and
tients with severe TBI, the two monitors detected 52 episodes subarachnoid hemorrhage. Elevations of the excitatory neuro-
in which SjvO2 decreased to less than 50% or PbtO2 decreased transmitter glutamate have been found in hypoxic-ischemic in-
to less than 8 mm Hg; of those 52 episodes, both monitored jury seen in low CBF, jugular venous bulb desaturation, seizures
variables fell below the ischemic threshold in 17, only SjvO2 and low CPP, and correlated with poor outcome in TBI. The
reflected ischemia in 19, and only PbtO2 reflected ischemia in magnitude of release of these substances correlates with the ex-
16 (Fig. 28.8) [83]. Ongoing research will determine the role of tent of ischemic damage. The time-dependent changes of these
PbtO2 monitoring and the relationship between PbtO2 moni- substances and the clinical implications are being evaluated,
toring and SjvO2 monitoring in critical neurologic illness. Re- and their incorporation into standard practice is being studied.
cent single-center prospective studies comparing brain tissue Certain issues related to quantification, bedside presentation
oxygen directed protocols in traumatic brain injury with his- of data, implantation strategies, and standardization of proto-
torical controls report reduced mortality as well as improved cols need to be addressed. An excellent review of the current
6-month clinical outcomes [84,85]. A randomized multicen- status, issues surrounding potential future developments and

25
[n = 13] *
20 Hyperventilation
15

10

5
Baseline

-5 FIGURE 28.7. The effect of hyper-


ventilation-induced hypocapnia on
-10 changes in mean arterial blood pres-
sure (MABP), intracranial pressure
(ICP), cerebral perfusion pressure
-15 * (CPP), end-tidal CO2 (ETCO2 ), PtiO2 ,
and jugular bulb oximetry (SjvO2 ).
-20 p < 0.05; before hyperventilation ver-
sus 10 minutes later. (From Unterberg
-25 * * AW, Kiening KL, Hartl R, et al: Mul-
timodal monitoring in patients with
* head injury: evaluation of the effects
-30
of treatment on cerebral oxygenation.
MABP ICP CPP ETCO2 PbtO2 SjvO2 J Trauma 42:S32S37, 1997, with per-
[mm Hg] [mm Hg] [mm Hg] [mm Hg] [mm Hg] [%] mission.)
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268 Section II: Minimally Invasive Monitoring

100 100 100


SjvO2 (%), PbtO2 (mm Hg)

80 80 80

60 60 60

40 40 40

20 20 20

0 0 0
Baseline Event Baseline Event Baseline Event Baseline Event Baseline Event Baseline Event
SjvO2 PbtO2 SjvO2 PbtO2 SjvO2 PbtO2
A B C
Both SjvO2 and PbtO2 decrease Only PbtO2 decreased below Only SjvO2 decreased below
below critical thresholds (17 cases) critical threshold (16 cases) critical threshold (19 cases)

FIGURE 28.8. Changes in jugular venous oxygen saturation (SjvO2 ) and brain tissue PO2 (PbtO2 ) dur-
ing 52 episodes of cerebral hypoxia/ischemia. The horizontal line across the box plot represents the
median, and the lower and upper ends of the box plot are the 25th percentile and 75th percentile, respec-
tively. The error bars mark the 10th and 90th percentiles. The closed circles indicate any outlying points.
A: Summary of the 17 cases in which both SjvO2 and PbtO2 decreased to less than their respective thresh-
olds, as defined in the text. B: Summary of the 16 cases in which PbtO2 decreased to less than the defined
threshold; but SjvO2 ; although decreased, did not decrease to less than 50%. C: Summary of the 19 cases
in which SjvO2 decreased to less than the threshold, but PbtO2 remained at greater than 10 torr. (From
Gopinath SP, Valadka AB, Uzura M, et al: Comparison of jugular venous oxygen saturation and brain
tissue PO2 as monitors of cerebral ischemia after head injury. Crit Care Med 27:23372345, 1999, with
permission.)

methodological aspects of microdialysis are discussed in detail but studies are not definitive [95]. Despite the promise and
in a recent article [91]. enthusiasm generated by NIRS, many problems remain with
the technology including tissue penetration, spatial and tem-
poral resolution, artifacts from subcutaneous blood flow and
methods of quantitative analysis which need to be resolved
NEAR-INFRARED SPECTROSCOPY [96]. Therefore, validation studies suggest that NIRS may be
more useful for qualitatively monitoring trends of brain tis-
Theoretically, the best monitor of brain oxygenation would be a sue oxygenation than for actual quantification and its cur-
noninvasive device that characterizes brain oxygenation in real rent clinical use is limited to a few centers and is adjunc-
time: near-infrared spectroscopy (NIRS) might eventually offer tive at best [93,97]. Some of the liabilities of near-infrared
the opportunity to assess the adequacy of brain oxygenation spectroscopy may be overcome by optoacoustic monitoring of
continuously and noninvasively, although to date the use of the cerebral venous saturation. Optoacoustic monitoring of cere-
technique in adults has been limited. bral venous saturation depends on the generation by near-
Near-infrared light penetrates the skull and, during trans- infrared light of ultrasonic signals in blood. The acoustic sig-
mission through or reflection from brain tissue, undergoes nals are then transmitted linearly through tissue and bone and
changes in intensity that are proportional to the relative con- provide a focused, depth-resolved signal that reflects venous
centrations of oxygenated and deoxygenated hemoglobin in oxygenation [98].
the arteries, capillaries, and veins within the field [92]. The
absorption (A) of light by a chromophore (i.e., hemoglobin)
is defined by Beers Law: A = abc, where a is the absorption
constant, b is the path length of the light, and c is the concen- NEUROIMAGING
tration of the chromophore, namely, oxygenated and deoxy-
genated hemoglobin. Because it is impossible to measure the Magnetic resonance imaging (MRI), positron emission spec-
path length of NIRS light in tissue, approximations as to rel- troscopy (PET) scans, cerebral angiography, and radionuclide
ative lengths and arterial versus venous contribution must be scans do not function as monitors per se. Rather, they are
made. indicated in response to suspicion of a new or progressive
Extensive preclinical and clinical data demonstrate that anatomic lesion, such as a subdural or intracerebral hematoma
NIRS detects qualitative changes in brain oxygenation [93]. or cerebral arterial vasospasm, that requires altered treatment.
Studies have been done comparing NIRS to other technologies Most neuroimaging modalities provide static, discontinuous
and assessing its correlation with EEG, transcranial Doppler, data and require moving a critically ill patient from the ICU to
PbtO2 and jugular venous O2 saturation changes. NIRS was a remote location. Even so, these techniques play an important
found to correlate with EEG, TCD, and PtO2 in transient cere- role in the overall management of patients with brain injury
bral hypoxia, subarachnoid hemorrhage, and during intraop- [99]. With the introduction of portable CT scanners and the
erative monitoring for carotid endarterectomy. It did not cor- development of ultrafast helical and spiral CT scanners, avail-
relate well with SjvO2 [94] values but was thought to provide ability and acquisition time for evaluations have significantly
complementary focal oxygenation data to SjvO2 s global oxy- decreased and can now be used for serial monitoring of ongo-
genation assessment. Clinical applications include traumatic ing neurologic processes and for evaluation of changes in CBF
brain injury where an rSO2 of less than 55% was thought to (see above).
suggest inadequate CPP and NIRS values were lower in the CT scans obtained at the time of admission to the hospital
high ICP group of patients vasospasm detection in the setting can provide valuable prognostic information. Marshall et al.
of subarachnoid hemorrhage, and the detection of intracra- [100] predicted outcome of head-injured patients in relation
nial hemorrhages such as subdural and epidural hematomas to four grades of increasingly severe diffuse brain injury and
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 28: Neurologic Multimodal Monitoring 269

TA B L E 2 8 . 4
OUTCOME AT DISCHARGE IN RELATION TO INTRACRANIAL DIAGNOSIS (% OF PATIENTS)

Outcome DI I DI II DI III DI IV Evacuated mass Nonevacuated mass

GR 27.0 8.5 3.3 3.1 5.1 2.8


MD 34.6 26.0 13.1 3.1 17.7 8.3
SD 19.2 40.7 26.8 18.8 26.0 19.4
PVS 9.6 11.2 22.9 18.8 12.3 16.7
Death 9.6 13.5 34.0 56.2 38.8 52.8
Total 100 100 100 100 100 100

GR, good recovery; MD, moderate disability; SD, severe disability; PVS, persistent vegetative state; DI, diffuse injury; DI categories I to IV represent
increasingly severe classes of diffuse brain injury.
From Marshall LF, Marshall SB, Klauber MR, et al: A new classification of head injury based on computerized tomography. J Neurosurg 75:S14S20,
1991, with permission.

the presence of evacuated or nonevacuated intracranial mass Diffusion Tensor Imaging has been found to be helpful in
lesions (Table 28.4). Normal CT scans at admission in patients further defining the anatomy of fiber tracts that have been
with GCS scores less than 8 are associated with a 10% to 15% damaged and has also been found to have prognostic value
incidence of ICP elevation [101,102]; however, the risk of ICP in severe TBI [106]. Functional MRI provides information re-
elevation increases in patients older than age 40 years, those garding neural activity, localization and the physiology of brain
with unilateral or bilateral motor posturing, or those with sys- function but is currently in use only for neurosurgical plan-
tolic blood pressure less than 90 mm Hg [101]. ning, brain mapping and in the investigation of neurobehav-
Although MRI often provides better resolution than CT ioral aspects and neuropsychologic sequelae of disorders such
scans, the powerful magnetic fields make the use of ferrous as Alzheimers disease, stroke, multiple sclerosis, brain tumors,
metals impractical (and dangerous), a ubiquitous component of and traumatic brain injury.
life-support equipment. To address this issue, MRI-compatible
ventilators, monitors, and infusion pumps have been devel-
oped, although the logistics of transport and the time re-
quired for scans continues to make this technique difficult MULTIMODAL MONITORING
for repeated monitoring. Recent advances in MRI technol- STRATEGIES
ogy, such as diffusion-weighted imaging, magnetic resonance
spectroscopy (carbon labeled, phosphorus labeled, and nitro- With technological advances and active ongoing research the
gen labeled), phase-contrast angiography, and functional MRI field of neurologic monitoring is developing rapidly. Multi-
provide information about oxidative metabolic pathways, cere- modal monitoring takes into account the limitations of each
bral blood volume, functional CBF, and neuronal activation monitoring modality and compensates by combining different
[99,103,104]. These techniques, while undergoing further eval- techniques into a generalized strategy that help to further eluci-
uation and validation, may one day prove useful in evaluat- date the pathophysiology and underlying cellular mechanisms
ing brain injury and its management. Recent clinical evidence of disease and focuses care on the physiologic aspects of dis-
of brain mitochondrial dysfunction after TBI, despite appar- ease. This concept is not new (consider the operating room and
ently adequate CDO2 , suggests that functional cellular evalu- the role of the anesthesiologist) and is becoming more common
ation and associated therapy may someday be as important as in the management of brain injury [107] as well as other neu-
maintaining CDO2 [105]. In addition to providing informa- rologic diseases. It is hoped that the use of these regimented
tion regarding ischemia and defining tissue at risk, MRI-based techniques will lead to improvements in patient outcome [108].

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CHAPTER 29 ECHOCARDIOGRAPHY
IN THE INTENSIVE CARE UNIT
ACHIKAM OREN-GRINBERG, SAJID SHAHUL AND ADAM B. LERNER

INTRODUCTION formation about the heart; systolic and diastolic function, cav-
ity size, and valvular function [1].
Echocardiography was introduced to the operating suite in the Ease of use, availability of diagnostic information within
1970s, with epicardial echocardiography as its initial applica- 10 to 15 minutes from the start of examination, high-
tion. Transesophageal echocardiography (TEE) during surgery quality imaging in most patients, and low complication
was first described in 1980 but did not become commonplace rates have all led to the pervasive use of echocardiography
until the mid-1980s. Since then, TEE has evolved to become in the perioperative environment and increasing use in the
a widely used and versatile modality for diagnosis and mon- ICU [28]. However, patient safety and optimal outcome
itoring of critically ill patients. As such, its use has expanded depend heavily on a thorough understanding of both the
into the perioperative period and the intensive care unit (ICU). strengths and limitations of the available technologies and their
Echocardiography provides both anatomic and functional in- applications.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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272 Section II: Minimally Invasive Monitoring

fying segmental and global left ventricular function. It records


BASIC TERMINOLOGY OF systolic and diastolic velocities within the myocardium and at
ECHOCARDIOGRAPHY the corners of the mitral annulus and is useful for studying
diastolic function and contractile asynchrony of the LV [10].
TECHNIQUES
A sonographer must use different echocardiographic imaging
Contrast Echocardiography
techniques and hemodynamic modalities to achieve a diagno- Contrast echocardiography is used to enhance the diagnostic
sis or management plan. The following is a list of the basic quality of the echocardiogram [11]. It may be used to improve
techniques used during an echocardiographic study. assessment of global function and regional wall motion abnor-
malities by 2D echocardiography. Although approved only for
LV opacification, recent clinical studies suggest a potential use
Two-Dimensional Echocardiography in assessing myocardial perfusion [12,13].

Two-dimensional (2D) echocardiography is the backbone of Transesophageal Versus Transthoracic


the echocardiographic examination [9]. Using 2D, a complete Echocardiography
visualization of the beating heart is achieved by displaying
Although transthoracic echocardiography (TTE) is a less inva-
anatomic structures in real-time tomographic images. By aim-
sive way to image cardiac structures, suboptimal acoustic win-
ing the ultrasound probe at the heart, exactly oriented anatomic
dows lead to low-quality images in many critically ill patients.
slices are obtained. Information acquired includes cardiac
These suboptimal acoustic windows are due to obesity, pul-
chamber sizes, global and regional systolic function, and valvu-
monary disease, the presence of chest tubes, drains and wound
lar anatomy.
dressings, and limitations on patient positioning. Using TTE in
the ICU can be challenging; one study found the echocardio-
graphic examination to be inadequate in approximately 50%
M-Mode Echocardiography of patients on mechanical ventilation and 60% of all ICU pa-
tients [8]. The relatively low percentage of adequate imaging
M-mode or motion-mode images are a continuous 1D graphic improves when TTE is used as a monitoring tool, which does
display that can be derived by selecting any of the individ- not require the same quality of images, and not as a diagnostic
ual sector lines from which a 2D image is constructed [9]. It tool. In a report of more than 200 ICU patients, TTE used as
is useful for quantification of myocardial wall and chambers a monitoring tool provided 2D images of acceptable quality in
sizes, which in turn can be used to estimate left ventricle (LV) 97% of patients [14].
mass and chamber volumes, respectively. Though very limited, In contrast to TTE, TEE is more invasive but consistently
M-mode can also be used to determine fractional shortening, a provides images of better quality. In up to 40% of patients, TEE
rough estimate of left ventricular systolic function. In addition, may provide additional unexpected diagnoses that are missed
since it has high temporal resolution, M-mode is helpful in as- by TTE [4,15]. Recent advances in ultrasound imaging, which
sessing the motion of rapidly moving cardiac structures such include harmonic imaging, digital acquisition, and contrast en-
as cardiac valves. docardial enhancement, have improved the diagnostic yield of
TEE [16,17].

Doppler Echocardiography
CONTRAINDICATIONS TO
Doppler echocardiography is used to supplement 2D and M-
mode echocardiography. It can provide functional information PERFORMING TEE
regarding intracardiac hemodynamics; systolic and diastolic
flows, blood velocities and volumes, severity of valvular le- Although TEE is safe [18,19], there are several contraindica-
sions, location and severity of intracardiac shunts, and assess- tions to probe insertion. These include significant esophageal
ment of diastolic function. The four types of Doppler modal- or gastric pathology; mass or tumors, strictures, diverticulum,
ities used include continuous-wave, pulsed-wave, color flow Mallory-Weiss tears, recent esophageal or gastric surgery, up-
mapping, and tissue Doppler [9]. Continuous-wave Doppler is per gastrointestinal bleeding, and dysphagia or odynophagia
used for measuring high-pressure gradient/high-velocity flows not previously evaluated. Esophageal varices are not an abso-
such as seen in aortic stenosis. When using continuous wave lute contraindication, and a riskbenefit analysis of each case
Doppler, the ultrasound probe continuously transmits and re- must be carried out before performing TEE in any individual
ceives sound waves. This increases the maximum limit of blood patient [20]. Practitioners must be aware of the potential for
velocity that can be evaluated before exceeding the Nyquist severe bleeding, in particular when a coagulation abnormality
limit. The Nyquist limit represents the maximum flow ve- exists. Cervical spinal injury is another relative contraindica-
locity that can be evaluated by Doppler and is dependent tion requiring careful riskbenefit analysis.
on both equipment and imaging variables. Continuous wave
Doppler can evaluate higher flows but does so at the expense
of spatial specificity. This is referred to as range ambigu- COMPLICATIONS AND
ity. Pulsed-wave Doppler is used for measuring lower-pressure SAFETY OF TEE
gradient/lower-velocity flows such as in mitral stenosis. In this
mode, the ultrasound probe sends out a pulse of sound and TEE is considered a moderately invasive procedure and com-
then waits to receive reflected waves. This lowers the Nyquist plications are rare. In one study of ICU patients, complica-
limit and the maximum velocities that can be interrogated but tion rates reached 1.6% and included hypotension following
allows for precise spatial resolution. Color flow mapping is sedation for probe insertion, oropharyngeal bleeding in a co-
useful for screening valves for stenosis or regurgitation, quanti- agulopathic patient, and aspiration during tracheal intubation
fying the degree of valvular regurgitation, imaging systolic and performed prior to TEE [19]. Another study in 2,508 ICU pa-
diastolic flow, and detection of intracardiac shunts. Doppler tients reported a complication rate of 2.6%. In this study, there
tissue imaging has been introduced as a new method of quanti- was no examination-related mortality. Complications included
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Chapter 29: Echocardiography in the Intensive Care Unit 273

transient hypotension or hypertension, circulatory deteriora- may often times be discerned from the echocardiographic eval-
tion, hypoxemia, arrhythmias, vomiting, coughing, superficial uation allowing for appropriate therapy to be initiated.
mucous membrane lesions, displacement of a tracheostomy
tube and accidental removal of a duodenal feeding tube [18]. A
large European multicenter study of 10,419 examinations re-
ported a complication rate of 2.5% with one (0.01%) case of Assessment of Left Ventricular
fatal hematemesis due to a malignant tumor [2]. In addition, in Systolic Function
0.88% of the reported cases, the TEE exam had to be prema-
turely terminated due to either patient intolerance or because Use of several echocardiographic assessment modalities is nec-
of cardiac, pulmonary, or bleeding events [2]. essary for evaluation of left ventricular systolic function. These
modalities include quantitative as well as qualitative assess-
Common Indications for TEE in the ICU ments.

In 1996, a task force created by the American Society of Anes-


thesiologists and the Society of Cardiovascular Anesthesiolo- Quantitative Assessment of Left
gists published guidelines regarding the indications for TEE Ventricular Systolic Function
[21]. Three categories of evidence-based clinical indications Volumetric Method Using Geometric Models. Quantitative as-
were identified. For indications grouped into category I, TEE sessment of left ventricular systolic function relies on volume
was judged to be frequently useful in improving clinical out- assessment using 2D tomographic images. To determine the
comes. To date, there is only a single category I indication for volume at end diastole (LVEDV) and end systole (LVESV),
TEE in the ICU. That indication is for unstable patients with the endocardial borders in two orthogonal tomographic planes
unexplained hemodynamic disturbance, suspected valve dis- are traced at end diastole and end systole. Several geometric as-
ease, or thromboembolic problems (if other tests or monitor- sumptions and formulas have been developed (e.g., truncated
ing techniques have not confirmed the diagnosis or patients ellipse, bullet formula, cylinder, and cone) to determine the
are too unstable to undergo other tests) [21]. This indica- LVEDV and LVESV based on these 2D images. Once LVEDV
tion, however, encompasses a significant proportion of ICU and LVESV have been determined, the stoke volume, and thus
patients and in practice, clinicians use echocardiography in cardiac output (CO) can be calculated:
the ICU for many other indications. These are summarized in
Table 29.1.
SV = LVEDV LVESV
CO = SV HR
ECHOCARDIOGRAPHIC In addition, ejection fraction (EF) can be calculated from
EVALUATION OF HEMODYNAMIC these volumes using the formula:
INSTABILITY
EF = SV/LVEDV 100%
Hemodynamic instability is an extremely common event in ev-
ery ICU. Determining the cause of such can sometimes be more These formulas work optimally in a symmetrically con-
challenging than one would expect. Echocardiography can be tracting ventricle; the presence of regional wall motion abnor-
used successfully in the diagnosis, monitoring, and manage- malities decreases accuracy. In addition, foreshortening of the
ment of the unstable patient in the ICU. Using echocardiogra- LV cavity is a common source of underestimation of LV end-
phy to determine the etiology of hemodynamic instability re- diastolic and end-systolic volumes and can similarly impact the
quires assessment of cardiac function, volume status, valvular accuracy of systolic function assessment with these formulas
function, and extracardiac processes. [1,22]. Lastly, since the models depend on accurate endocardial
border definition, their use requires adequate visualization. In-
complete endocardial definition is described in 10% to 20%
of routine echocardiographic studies [23] and may reach 25%
ASSESSMENT OF CARDIAC in ICU patients [24]. This challenge is even greater in patients
FUNCTION requiring mechanical ventilation in which imaging can be par-
ticularly challenging. These challenges have limited the use of
Systolic dysfunction of either ventricular chamber must be con- the geometric models and formulas for assessment of LV sys-
sidered in every unstable patient. The etiology of dysfunction tolic function.

Discs Method (Simpsons Rule). Another method for volumet-


TA B L E 2 9 . 1 ric assessment of LV systolic function is the discs method, which
COMMON INDICATIONS FOR PERFORMING TEE may be more accurate than the other volumetric methods de-
IN THE ICU scribed above, particularly in the presence of distorted LV ge-
ometry [9]. In this method the ventricle is divided into a series
Assessment of LV systolic Evaluation of valvular of discs of equal height and each disc volume is calculated as
function pathology follows:
Hemodynamic management Determination of source of
emboli Disc volume = disc height disc area
Evaluation of pericardial Evaluation of endocarditis
tamponade The ventricular volume can be calculated from the sum of
Evaluation of pulmonary Evaluation of chest trauma the volumes. This technique requires true apical images, which
embolism in clinical practice may be difficult to achieve. Foreshortening
Evaluation of aortic dissection Evaluation of hypoxemia of the ventricular apex will result in inaccurate assessment of
the left ventricular EF and CO (Fig. 29.1).
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274 Section II: Minimally Invasive Monitoring

ESV (A4C) 56 mL
EDV (BP) 81 mL

A B

FIGURE 29.1. Calculation of cardiac output using the disc method (Simpsons rule). TEE Mid-esophageal
4-chamber view in diastole (A) and systole (B) is shown. Using the Simpsons rule, LVEDV (81 mL) and
LVESV (56 mL) were calculated by the echocardiographic computer. From these volumes, the cardiac
output was calculated to be 1.7 L/min (8156 mL) 69 beats per minute.

Qualitative Assessment of Left Ventricular ities in all coronary arterial circulatory beds as well as rudimen-
Systolic Function tary evaluation of volume status [26]. However, it is important
to remember that this view alone is never satisfactory for as-
2D Evaluation of Ventricular Systolic Function. Using 2D sessing overall systolic function.
imaging, two of the most important questions regarding hemo-
dynamic stability can be rapidly answered; are the ventricles
contracting well and are they adequately filled. Using 2D, an
experienced observer can qualitatively evaluate systolic func- Regional Left Ventricular Function
tion. This should be assessed from multiple tomographic planes
and attention must be given to obtaining adequate endocardial Most commonly, abnormal regional wall motion is the result of
definition. Normal ventricular contraction consists of simul- coronary artery disease and resultant ischemia/infarction. Ab-
taneous myocardial thickening and endocardial excursion to- normal wall motion is a continuum of conditions consisting of
ward the center of the ventricle. It is important to look for this hypokinesis, akinesis, and dyskinesis. With dyskinesis, the af-
myocardial thickening; infarcted myocardium may be pulled fected wall segment moves away from the center of the ventricle
inward by surrounding, normal myocardium. There is some during systole. To standardize echocardiographic evaluations
regional heterogeneity of normal wall motion with the prox- of wall motion, a 17-segment model of the LV has been defined
imal lateral and inferolateral (or posterior) walls contracting [25]. These 17 segments are evaluated separately for the pres-
somewhat later than the septum and inferior wall [25]. For ence and degree of regional wall motion abnormality. When
qualitative assessment of overall systolic function, the echocar- the etiology of the wall motion abnormality is CAD, the loca-
diographer integrates the degree of wall thickening and endo- tion of the coronary lesion can be usually predicted from the
cardial motion in all tomographic views and reaches a con- location of the regional wall motion abnormality.
clusion about overall LV systolic function and EF. Although
different institutions use different standards, severe LV systolic
dysfunction is usually defined as an EF <30%, moderate dys-
function 30% to 45%, mild depression 45% to 55%, and nor- Contrast Echocardiography
mal >55%. This method of EF estimation is of great clinical
utility and can be performed with good correlation to quantita- Recent innovations have been made to overcome some of the
tive measurements. There are however, a few potential pitfalls technical obstacles related to endocardial border detection and
to 2D assessment of EF that must be considered: image quality. Intravenous echocardiographic contrast agents
that opacify the left side of the heart can markedly improve
1. Accurate assessment requires satisfactory endocardial bor- visualization of the LV cavity and enhance endocardial defini-
der definition. Qualitative EF estimation becomes inaccu- tion. These agents can aid assessment of regional and global LV
rate when the endocardium is inadequately defined. functions [2730]. They also have the potential to salvage
2. Accurate estimation of EF depends on the experience of the nondiagnostic TTEs in ICU patients. One study demonstrated
echocardiographer. a salvage rate of 51% [31] and another 77% of nondiag-
3. In asynchronous contraction (paced-rhythm, conduction nostic TTEs [32]. In addition to improving visualization and
defects, etc.), assessment of EF is more difficult. assessment of LV function, assessment of myocardial perfusion
defects with intravenous contrast has been reported with vari-
Despite its limitations, 2D qualitative assessment is the most ous imaging techniques and modalities [3335].
widely used technique for assessment of LV systolic function
due to its ease of application in the clinical setting. In the op- Doppler Assessment of Left Ventricular
erating room, after completing the TEE exam, most physicians
monitor LV systolic function continuously with 2D imaging
Systolic Function
using the transgastric (TG) midpapillary short-axis view. This Doppler spectral profiles can be used to evaluate left ventric-
allows for quick assessment of regional wall motion abnormal- ular function quantitatively. This evaluation of left ventricular
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Chapter 29: Echocardiography in the Intensive Care Unit 275

systolic function is based on calculation of stroke volume (SV) equals 1. Deviations up to 20 degrees in intercept angle are
and CO. acceptable since only a 6% error in measurement is intro-
Stroke Volumethe volume of blood ejected during each duced.
cardiac cycle is a key indicator of cardiac performance. SV can 3. Velocity and diameter measurements should be made at the
be calculated by using pulse wave Doppler (PWD) to measure same anatomic site. When the two are measured at different
the instantaneous blood velocity recorded during systole from places, the accuracy of SV and CO calculations is decreased.
an area in the heart where a cross-sectional area (CSA) can be 4. Although the pattern of flow is assumed to be laminar, in
easily determined. The left ventricular outflow tract (LVOT) is reality the flow profile is parabolic. This does have some im-
most commonly used because its cross section is essentially a pact on velocity-based calculations [25]. However, in rou-
circle. By measuring the diameter of the LVOT and assuming a tine clinical practice this factor is of little significance and
circular geometry, the CSA is calculated as (D/2)2 . Any car- can be essentially ignored.
diac chamber or structure that has a measurable CSA may be
used; mitral valve annulus, right ventricular outflow tract out- Determination of Left Ventricular dP/dt
flow, and tricuspid annulus are some examples. By tracing the
outline of the PWD profile, the echocardiographic computer The changing rate of left ventricular pressure (dP/dt) is an
can calculate the integral of velocity by time or the velocity important parameter in the assessment of myocardial systolic
time integral (VTI). The VTI is the distance (commonly referred function. Traditionally, dP/dt was derived from the left ven-
as the stroke distance) that the average red cell has traveled tricular pressure curve acquired at cardiac catheterization us-
during the systolic ejection phase. SV (cm3 ) is then calculated ing a micromanometer catheter recording. It has been shown
by multiplying the VTI (stroke distance in cm) by the CSA in that echocardiography can be used accurately and reliably to
cm2 of the conduit (i.e., LVOT, aorta, mitral valve annulus, pul- assess dP/dt by performing Doppler assessment of mitral regur-
monary artery) through which the blood has traveled [3642]; gitant jet [45,46]. Using continuous wave Doppler, a spectral
SV = CSA VTI. CO is then easily derived by multiplying display of the mitral regurgitation (MR) jet is obtained. From
the calculated SV by the heart rate: CO (cm3 /min) = SV HR the spectral display, information about the rate of pressure de-
(Fig. 29.2). velopment within the LV can be derived using measurements
This approach to SV and CO calculations has shown very undertaken in the early phase of systole (the upstroke of the
good correlation with thermodilution-derived CO measure- velocity curve is used for calculations). Determination of dP/dt
ments [43]. There are however, several potential sources of error: using the MR spectral jet is done by calculation of the time re-
quired for the MR jet velocity to go from 1 m per second to
3 m per second. The time between these two points represents
1. CSA determination often leads to the greatest source of er- the time that it takes for a 32 mm Hg pressure change to oc-
ror. When using any diameter for CSA determination, any cur in the left ventricular cavity. This is based on the modified
error in measurement will be squared (CSA = (D/2)2 ). This Bernoulli equation (P = 4v2 ), which relates pressure to velocity.
translates to a 20% error in calculation of CO for each 2- Thus, in going from 1 m per second to 3 m per second:
mm error when measuring a 2.0-cm diameter LV outflow
tract [25]. Studies have shown that while the Doppler ve- P = 4vB2 4vA2 (4(32 ) 4(12 ) = 32)
locity curves can be recorded consistently with little interob-
server measurement variability (2% to 5%), the variability where vB is velocity of 3 m/s.
in 2D LVOT diameter measurements for CSA is significantly dP/dt is then is calculated using the formula:
greater (8% to 12%) [44]. dP/dt = 32 mm Hg time (seconds).
2. The Doppler signal is assumed to have been recorded at a
parallel or near parallel intercept angle, called , to blood A depressed ventricle will take a longer time to develop
flow. The Doppler equation has a cos term in its denom- this pressure gradienta lower dP/dt. Normal dP/dt value
inator. With an intercept angle of 0 degree, the cos term is >1,200 mm Hg per second (or time 27 milliseconds),

A B

FIGURE 29.2. Calculation of CO using spectral Doppler approach. A: Mid-esophageal long-axis view of
LVOT. LVOT measurement is 2.0 cm. The CSA is calculated as (D/2)2 to be 3.14 cm2 . B: Transgastric
long-axis view using a PWD directed through the aortic valve opening. VTI is calculated by the computer
through tracing the outer envelope of the spectral signal and is determined to be 14.6 cm. SV is the product
of CSA and VTI: 3.14 14.6 = 46 mL. CO = SV HR: 46 61 = 2.8 L/min.
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276 Section II: Minimally Invasive Monitoring

moderately depressed systolic function value range between volume is increased. Conversely, using lung-protective ven-
1,000 and 1,200 mm Hg per second, and when dP/dt is de- tilation with low tidal volume may lead to minimal pleural
creased bellow 1,000 mm Hg per second, left ventricular sys- pressure changes over a single respiratory cycle. In this case,
tolic function is severely depressed [47,48]. inspiration will not induce any significant change in LV SV,
even in fluid-responsive patients (leading to a false-negative
reading). This may explain why the SVV has been found
ASSESSMENT OF PATIENT to be a reliable predictor of fluid responsiveness in patients
with tidal volume ranging between 8 and 15 mL per kg
VOLUME STATUS [49,55,56].
One of the most challenging and crucial tasks in the manage- Three echocardiographic indices have been shown to reli-
ment of a hemodynamically unstable patient is to predict ac- ably assess fluid responsiveness based on the dynamic param-
curately whether the patient would benefit from fluid therapy. eter approach:
Overhydration may lead to pulmonary edema, hypoxia, and
worsening outcome and therefore should be avoided. A novel 1. Aortic Flow Index: The increase in SV during positive pres-
and effective method for determining this fluid responsive- sure ventilation as described earlier leads to increased peak
ness is through the assessment of dynamic parameters. Ex- flow across the LVOT, the aortic valve and descending aorta.
amples of such dynamic parameters are stroke volume variation Similarly, the decrease in SV during exhalation leads to de-
(SVV) and pulse pressure variation (PPV). These parameters crease in peak flow across these structures. The aortic flow
can be readily assessed with echocardiography. index can efficiently predict fluid responsiveness in patients
SVV and PPV are caused by the interaction of the cardiac ventilated with positive pressure. To calculate the aortic flow
and respiratory systems; that is, the changes in intrathoracic index, one has to use the pulse wave Doppler to sample flow
pressure during controlled ventilation have an impact on SV at the ascending aorta. This will generate a series of peak
and therefore, arterial pressure. The increase in intrathoracic flow spectral displays that are increased during inspiration
pressure during the inspiratory phase of positive pressure venti- and decreased during exhalation (Fig. 29.3). The formula
lation leads to simultaneous but different physiologic effects on to calculate the aortic flow index is
the left and right sides of the heart. In the left side, SV increases Aortic flow index
as blood is pushed forward out of the pulmonary veins into
= (PEAK maxins PEAK minexp )/mean 100
the LV. In addition, the increased intrathoracic pressure leads
to improved afterload matching for the LV, which increases An index of >12% has been shown to discriminate
SV by functionally decreasing afterload. The interventricular between fluid responders and nonresponders with high
septum is shifted toward the right ventricle (RV) also increas- sensitivity and specificity (100% and 89%, respectively)
ing LV SV. On the right side, right ventricular inflow decreases [57]. This index can be calculated rapidly by either TTE
secondary to compression of the inferior vena cava (IVC). The or TEE.
rightward shift of the septum also decreases RV SV. At the be- 2. Superior Vena Cava Collapsibility Index: This concept is
ginning of the exhalation phase, SV decreases since both the similar to other dynamic parameters. During the inspiratory
pulmonary veins and the RV are relatively empty. In hypo- phase of positive pressure ventilation, the superior vena cava
volemic patients, the magnitude of these cyclical or dynamic (SVC) collapses due to increase in the intrathoracic pres-
changes is increased and this serves as the basis for the accu- sure. The SVC re-expands back to its baseline during exha-
rate assessment of fluid responsiveness using these parameters lation. The degree of collapsibility depends on the degree of
[4954]. hypovolemia; as less volume circulates in the intravascular
In addition to preload, other factors affecting SVV and compartment the SVC will be susceptible to the increase in
PPV include chest wall compliance and ventilation parame- intrathoracic pressure, and thus this phenomenon is exac-
ters, including tidal volumes and airway pressures. In situations erbated in a state of hypovolemia. The SVC index can be
wherein chest wall compliance and respiratory parameters are calculated with TEE only by using either 2D or M-mode
held relatively constant, SVV can be used as a guide to estab- modality to measure the SVC diameter during PPV (Fig.
lishing whether a given patient will respond to fluid loading by 29.4). The formula to calculate this index is
increasing CO.
Limitations to this technique include the following: SVC collapsibility index
= (Dmaxexp Dminins )/Dmaxexp 100
1. Need for positive pressure ventilation with either total paral-
ysis or heavy sedation preventing from the patient to initiate An index of >36% has been shown to predict fluid re-
the ventilator. sponsiveness with high sensitivity and specificity (90% and
2. Effect of cardiac rhythm. In patients with cardiac arrhyth- 100%, respectively) [58] and can be very useful in predict-
mia, the beat-to-beat variation in SV and hence in BP may ing the need for fluid therapy in hemodynamically unstable
no longer reflect the effects of mechanical ventilation. This patients.
is particularly true in patients with atrial fibrillation or fre- 3. Inferior Vena Cava Collapsibility Index: The rationale be-
quent extrasystoles. In patients with few-and-far-between hind the IVC collapsibility index is similar to other dynamic
extrasystoles, the arterial pressure curve can still be ana- parameters. The physiology, however, is slightly different.
lyzed if the cardiac rhythm is regular during at least one The increased intrathoracic pressure during positive pres-
respiratory cycle. sure ventilation as compared to the extrathoracic pressure
3. Effect of tidal volume. Increasing tidal volume will result leads to reduced pressure gradient to venous return. This,
in increasing the mean airway pressure and, hence, in de- in turn, leads to decrease in systemic venous return and as a
creasing the mean cardiac preload (leftward shift on the consequence to increase in the volume of the extrathoracic
FrankStarling curve). Therefore, a patient operating on the venous blood. The end result is an increase in extrathoracic
flat portion of the FrankStarling curve (i.e., insensitive to IVC diameter during positive pressure breath, followed by
changes in preload) may operate on the steep portion and a decrease in its diameter during exhalation [59,60]. Re-
hence become sensitive to changes in preload (in essence cently, IVC collapsibility during positive pressure ventilation
leading to false-positive reading of this index) if the tidal has been used to predict fluid responsiveness similar to the
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Chapter 29: Echocardiography in the Intensive Care Unit 277

FIGURE 29.3. TEE deep transgastric view assessment of aortic flow index. The pulse-wave Doppler
sample volume is positioned at the LVOT level, demonstrating spectral displays of peak flows during PPV.
The peak flows vary with respiration; increased during positive pressure breath (1) and decreased during
exhalation (2). The aortic flow index is calculated as the difference between the peaks flows divided by
their mean. In this example, the aortic flow index = (PEAK maxins PEAK minexp )/mean 100 = (1.12
0.88/1) 100 = 24%. This indicated severe hypovolemia and fluid resuscitation initiated.

aortic flow index and other dynamic parameters [61]. In thus estimate preload. These measurements can be com-
this study, the change in IVC diameter during positive pres- pared with reported estimates of normal ventricular dimen-
sure ventilation (DIVC ) was defined as the difference be- sions to define degrees of ventricular enlargement. A single
tween the maximum and the minimum IVC diameter over measurement, however, is of limited value in defining the
the mean and expressed as percentage: DIVC = (DIVCmax preload state of any given patient. A patient with a history
DIVCmin )/mean 100%. In this study, a threshold DIVC of cardiomyopathy, as an example, will have an increased
value of 12% allowed identification of fluid responders with LV end-diastolic diameter compared to a normal patient. To
positive and negative predictive values of 93% and 92%, define such a patient as having adequate or excess preload
respectively. To assess for IVC collapsibility, the IVC is vi- is not justifiable. Serial measurements of LV diameter are
sualized in the subcostal view, and the IVC diameter is mea- more useful clinically in assessing changes over time and in
sured 3 cm from the right atrium by either 2D or M-mode response to therapies such as intravenous fluid challenge or
technique. diuresis. A number of studies that have compared echocar-
diographic estimates of preload with PAOP have shown the
potential superiority of the echocardiographic method [62
ASSESSMENT OF LEFT 64]. This method seems to perform well in detecting de-
VENTRICULAR PRELOAD creased end-diastolic volumes and hypovolemia. However,
when used to diagnose high preload or fluid overload, they
Preload is defined as the myocardial fiber length at end diastole may not be as reliable [43]. In the operating room, both
[43]. LV end-diastolic volume (LVEDV) is one of several clinical end-diastolic areas and volumes correlated well with ther-
variables used to assess preload. Accurate preload estimation modilution cardiac index in patients undergoing coronary
is one of the main challenges faced when caring for critically ill artery bypass grafting [65] and liver transplantation [66],
patients, even to the most experienced physician. Traditionally, while PAWP showed no correlation.
preload has been assessed using physical examination, clinical B. Pulsed Wave Doppler Method: Preload estimation can be
assessment of end-organ perfusion, and direct measurement assessed by Doppler echocardiography. The velocity profile
of intravascular pressures. Echocardiography can be used effi- of blood flow through the mitral valve during diastole is
ciently to supplement clinical assessment. normally biphasic. In a young individual with normal LV
compliance and relaxation, the early, passive filling phase,
A. 2D Echo Method: LV diameter measured with 2D echo represented by the E-wave, exceeds the component of filling
can be used to extrapolate LV volume at end-diastole, and due to atrial contraction, represented by the A-wave. The
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278 Section II: Minimally Invasive Monitoring

FIGURE 29.4. TEE upper esophageal view of the superior vena cava M-mode. SVC collapsibility index
= (Dmaxexp Dminins )/Dmaxexp 100 = (2.1 1.1)/2.1 100 = 47%, indicating hypovolemia and
fluid responsiveness.

magnitude of theses flows and their ratio varies with age in


normal individuals [25] (Fig. 29.5). EVALUATION OF RIGHT
VENTRICULAR FUNCTION
Using the peak E/A velocity ratio, LV end-diastolic pres-
sure (LVEDP) can be roughly estimated. With this technique, a
AND PRELOAD
ratio >2 is associated with LVEDP >20 mm Hg [67]. It is pos- Right ventricular systolic dysfunction is another potential cause
sible to estimate PAWP more accurately by using the equation of hypotension. In practice, estimates of RV function are made
[68]: from qualitative assessments of 2D imaging. Using either TEE
(mid-esophageal four-chamber view) or TTE (apical and sub-
PAWP = 18.4 + [17.1 ln(E peak/Apeak)] costal views), the right ventricular free wall can be visualized
and its thickening and displacement can be noted. In situa-
One study demonstrated that measurement of transmitral tions where right ventricular dysfunction is the sole cause of
and pulmonary venous flows by Doppler can be used to es- hypotension, whether directly from states causing myocardial
timate LV-filling pressure in critically ill patients under me- dysfunction or as a result of a secondary issue such as a pul-
chanical ventilation [69]. In this study, an E/A ratio >2 had a monary embolus, the LV is typically underfilled. Preload of
positive predictive value of 100% for a PAWP value >18 mm the RV is also estimated from either qualitative or quantitative
Hg. However, a large E/A ratio may also be seen in young assessment of ventricular size while again understanding that
healthy subjects. In this population, LV elastic myocardial re- single measurements of such dimensions are of limited useful-
laxation is rapid, which allows for almost complete LV filling ness.
during early diastole. This can lead to high E/A ratio with-
out elevation of left atrial (LA) pressure [70]. Therefore, any
interpretation of transmitral flow must take into account the
patients age. In addition, heart rate also modifies the trans-
mitral flow pattern. Since tachycardia shortens diastolic filling
ASSESSMENT OF VALVULAR
time, atrial contraction may occur before early filling is com- ETIOLOGIES OF HEMODYNAMIC
pleted. This will potentially result in a higher peak A-wave INSTABILITY
velocity than when the heart rate is slower. Furthermore, the
transmitral E- and A-waves can overlap, making interpretation Abnormalities of valvular function can, on occasion, be the
of the transmitral indices impossible [71]. Thus, in tachycardic primary cause of hypotension. Although valvular stenoses
patients a low E/Aratio does not necessarily relate to a low can certainly have impact on hemodynamics in the ICU pa-
PAOP. tient, they are rarely the direct cause of hypotension. For this
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Chapter 29: Echocardiography in the Intensive Care Unit 279

A B

FIGURE 29.5. A: Schematic representation of transmitral inflow profile showing E- and A waves during
diastole. B: TEE mid-esophageal four-chamber view of transmitral inflow showing E- and A waves.

reason, this section will concentrate on evaluation of regurgi- annulus, to prolapse wherein the excursion of a leaflet tip is
tant valvular lesions. above the level of the mitral annulus during systole, to flail,
where a leaflet flows freely into the left atrium, frequently
as a consequence of ruptured chordae tendineae. Typically,
the MR jet is eccentrically directed away from the affected
Echocardiographic Evaluation of leaflet.
Mitral Regurgitation Class IIIRestrictive leaflet motion: Characterized by re-
striction of the leaflet, most commonly as a result of left
Echocardiographic evaluation of MR includes assessment of ventricular dilation that displaces the papillary muscle away
valve anatomy, severity of regurgitation, LA enlargement due from the mitral valve annulus and in this way prevents
to volume overload, ventricular function, and the severity leaflet coaptation. The direction of the MR jet may be cen-
of pulmonary arterial hypertension. The mitral apparatus in- tral or eccentrically directed toward the side of the more
cludes the anterior and posterior leaflets, the annulus, chor- affected leaflet. Mitral valvular systolic anterior motion
dae tendineae, and the papillary muscles with their supporting (SAM), which is discussed later, is also considered as an ex-
LV walls. The etiology of MR could be a result of anatomical ample of restricted leaflet motion
or functional changes in the mitral valve and its supporting
structures. Anatomical changes in mitral valve leaflet pathol-
ogy can be caused by rheumatic disease, endocarditis, myx-
omatous disease, infiltrative diseases, such as amyloid, sar-
Mitral Regurgitation Assessment
coid, mucopolysaccharidosis, and collagen-vascular disorders, 1. 2D Examination: Basic 2D assessment may provide clues
such as systemic lupus erythematosus and rheumatoid arthri- for the presence of MR. Structural leaflet abnormality or
tis. Functional changes in the mitral annulus leading to dila- coaptation defects may be obvious in some cases. Indirect
tion, secondary to LA as well as LV dilation, may result in signs of MR should also be sought. These include LV and LA
MR due to incomplete leaflet coaptation. MR can also oc- enlargement and signs of pulmonary arterial hypertension;
cur as a result of chordal tear or elongation, which leads to elevated PA pressures estimated from Doppler interrogation
inadequate tensile support of the closed leaflet(s) in systole of Tricuspid regurgitation (TR) jets as an example.
with prolapse of the leaflet(s) into the left atrium [44]. Pap- 2. Doppler Flow Examination: Doppler flow examination is
illary muscle rupture can occur in the setting of acute myocar- the most common method used to screen and evaluate MR.
dial infarction and frequently leads to cardiogenic shock from MR is graded as trivial, mild, moderate, or severe, which
acute, severe MR. Partial rupture is more common and better corresponds to the angiography scores of 1+, 2+, 3+, and
tolerated. 4+. A visual assessment of the area of the MR color map
The Carpentier classification is commonly used to define provides a rough estimate of the severity of regurgitation.
the pathophysiologic mechanism leading to the regurgitation: However, this simple visual assessment has limitations. As
normal, restrictive, or excessive leaflet motion [72]. an example, eccentric MR jets that run along an LA wall
may appear less severe (the Coanda effect). In addition,
Class INormal leaflet motion: the most common cause color gain settingsa technical issuecan have significant
of MR wherein leaflet motion is normal and there is mitral impact on the size of the MR color map. Low color gains
annular dilation and papillary muscle dysfunction due to will increase the size where as high gains will reduce it. This
myocardial ischemia. In most cases, the MR jet is centrally is sometimes referred to as the dial-a-jet phenomenon.
directed into the left atrium. Typically, color flow velocity limits should be set in the
Class IIExcessive leaflet motion: Characterized by exces- 50 to 60 cm per second range when evaluating MR. As
sive leaflet motion ranging from leaflet billowing wherein mentioned in the prior section, MR jet direction has im-
a portion of a leaflet projects above the annulus in sys- portant clinical implications. Centrally directed jets usually
tole while the coaptation point remains below the mitral result from annular dilation or ischemic and dysfunctional
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280 Section II: Minimally Invasive Monitoring

papillary muscle. Eccentric jets are caused almost exclu- diseases of the valve leaflets include degenerative calcification,
sively by structural abnormalities of the mitral apparatus. rheumatic fever, infective endocarditis, and congenital bicuspid
As a consequence, eccentric jets are unlikely to improve after aortic valve (which is usually associated with aortic stenosis)
improving myocardial ischemia. [75]. Dilation of the ascending aorta and aortic root may be
due to chronic hypertension, aortic dissection, degenerative dis-
eases of the aorta, cystic medial necrosis, Marfans syndrome,
Quantification of Mitral Regurgitation and several rare conditions including ankylosing spondylitis,
and syphilitic disease.
A. Vena Contracta Width: The vena contracta is the narrow
contracted portion of the MR jet seen just below the mitral
leaflets. The width of this jet has been shown to correlate Evaluation of Aortic Regurgitation Severity
well with the severity of MR [73]. Widths of <3 mm corre-
spond to mild MR, 3 to 5 mm with moderate MR, and more A. Jet Width/LVOT Diameter Ratio: By viewing the LVOT in
than 7 mm with severe MR [74]. Limitation includes the sit- the long axis, the regurgitant jet width can be qualitatively
uation where there are multiple MR jets or the presence of compared with the diameter of the LVOT. A ratio of 1%
eccentric jets. to 24% is considered trivial AR (0 to 1+ ), 25% to 46%
B. Pulmonary Vein Flow Reversal: Blunting or reversal of the mild AR (1+ to 2+ ), 47% to 64% moderate (2+ to 3+ ),
systolic component of pulmonary venous inflow is one of and >65% severe (3+ to 4+ ) AR [76]. An alternate method
the most reliable signs of hemodynamically significant MR. is the use of M-mode, where the Doppler beam is placed
Systolic flow reversal is associated with severe MR whereas perpendicular to the outflow tract. The regurgitant jet can be
blunting is usually associated with moderate or moderate- seen within the LVOT boundaries during diastole. Dividing
to-severe MR. Limitations includes the inability to use this the regurgitant jet width by the LVOT width can then be
in the presence of atrial fibrillation where there is systolic used as outlined to grade the AR.
blunting of flow due to loss of atrial relaxation, independent B. Jet Area/LVOT Area Ratio: Using a short-axis view of the
of the degree of MR. aortic valve, the area of the regurgitant jet can be compared
C. Proximal Isovelocity Surface Area Method (PISA): The with the area of the LVOT. A ratio of <4% is considered
PISA method is based on the principle that a regurgitant jet trivial AR (0 to 1+ ), 4% to 24% mild (1+ to 2+ ), 25% to
accelerates in layers of concentric shells proximal to the re- 59% moderate (2+ to 3+ ), and >60% severe (3+ to 4+ ) AR
gurgitant orifice. Immediately adjacent to the orifice, these [77].
shells have small area with high-velocity flow and at in- C. Vena Contracta: The vena contracta width of an aortic in-
creasing distance from the orifice they have larger area and sufficiency (AI) jet can be measured in the long-axis view
lower velocities [44]. By interrogating this area with color of the jet. A vena contracta width of more than 6 mm has
Doppler, the regurgitant volume can be calculated. The re- been associated with severe AR [78].
gurgitant volume of blood is the product of the shell area D. Slope of Aortic Regurgitant Jet Velocity Profile: The veloc-
(PISA) and the aliasing velocity. Since this regurgitant vol- ity of the regurgitant jet is directly correlated to the pres-
ume is passing through a defect in the mitral valve, the re- sure gradient between the aorta and the LV in diastole. The
gurgitant orifice area (ROA) can be calculated as follows: more severe the AR, the faster the velocity profile will ap-
ROA = regurgitant volume VTIMRjet . proach zero as the gradient between the aorta and the LV
decreases rapidly. Using this principle, the slope of the rate
Systolic Anterior Motion: SAM of the mitral valve repre- of decay of the velocity jet can be used as a measure of
sents an important diagnosis that must be considered in the regurgitation severity. A measurement of the pressure half
unstable patient. MV SAM is caused when a venturi effect time of this decay (the time interval between maximal AR
of blood flow at high velocity through a narrowed space be- gradient and the time it takes to half the maximal gradi-
tween the anterior mitral valve leaflet and LV septum causes ent). A pressure half-time of less than 200 ms corresponds
the MV leaflet(s) to be displaced toward the LVOT, causing ob- to severe, 200 to 500 ms moderate, and >500 ms mild AR
struction to systolic flow. Patients at risk for developing SAM [79,80]. A potential pitfall of this grading technique is that
include those with hypertrophied LV septums, whether asym- it may be influenced by other pathologies that influence
metric or symmetric, patients with small LV diameters, patients the gradient between the aorta and LV, such as diastolic
with redundant mitral apparatus tissue and patients with hy- dysfunction.
percontractile left ventricles. 2D imaging of the mitral leaflet
and LVOT will show movement of the leaflet into the path of
blood flow. Color Doppler imaging will reveal color alias-
ing of blood flow, the Doppler equivalence of turbulence, Assessing Tricuspid Regurgitation
in the LVOT. In addition, SAM frequently prevents normal
coaptation of the mitral leaflets resulting in significant, usually Tricuspid regurgitation may be the result of leaflet abnormal-
anteriorly directed, eccentric MR. Continuous wave Doppler ities due to myxomatous disease or destruction from endo-
interrogation of the outflow tract from deep gastric windows carditis. More frequently, increases in TR may be secondary
will reveal a high-velocity flow profile, often dagger shaped, to processes that impact right ventricular and tricuspid annu-
which can be used to quantify a pressure gradient across the lar dimensions. Such examples include both acute and chronic
obstruction. The response of this process to therapeutic inter- volume overload and acute and chronic increases to RV after-
ventions can be followed using these echocardiographic assess- load. Examples of the latter include pulmonary embolus and
ments. primary or secondary pulmonary artery hypertension. TR is
typically quantified by assessing color map area and with vena
contracta width as described in the assessment of MR. Evalu-
Assessing Aortic Regurgitation ation for RV enlargement and systolic function is important.
Continuous wave Doppler interrogation of the TR jet allows
Causes of aortic regurgitation (AR) can be divided into ab- for quantification of systolic pulmonary arterial pressures and
normalities of the aortic valve leaflets and the aorta. Primary partial assessment of RV afterload. This is performed by adding
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Chapter 29: Echocardiography in the Intensive Care Unit 281

an actual or estimate of CVP to the maximum pressure of the


TR jet.

EXTRACARDIAC CAUSES OF
HEMODYNAMIC INSTABILITY
Pericardial Tamponade
Cardiac tamponade is a clinical and hemodynamic diagno-
sis; echocardiography may however, be assistance in equivocal
cases. Chronic, or slowly accumulating effusions can become
very large (>1,000 mL) without significant increase in pericar-
dial pressures. In the acute setting, however, even a small vol-
ume of fluid (50 to 100 mL) may lead to significant increase in
pericardial pressure and tamponade physiology. The echocar-
diographic diagnosis of tamponade first requires demonstra-
tion of an effusion. From there, the examination should
focus on identifying cardiac chamber collapse. As the pericar- FIGURE 29.7. Transthoracic echocardiography subcostal view focus-
dial pressure increases, the cardiac chambers will show col- ing on the right atrium demonstrating a mobile mass in the atrium
lapse in sequence from lowest pressure to highest; the atria will making the diagnosis of emboli in transit in a patient with acute car-
diovascular collapse. RA, right atrium; TV, tricuspid valve.
collapse first, followed by the RV and then LV. Furthermore,
the collapse of each chamber will be most pronounced dur-
ing the portion of the cardiac cycle during which the pressure
is the lowest in that chamber; ventricular systole for the atria is nondiagnostic and the clinician has high level of suspicion,
and ventricular diastole for the ventricles. This collapse can be or there is evidence of RV overload or hemodynamic instabil-
evaluated with M-mode interrogation of the chamber walls. ity, TEE examination is indicated [81]. In these circumstances,
Pulsed-wave Doppler echocardiographic interrogation of ven- TEE has a sensitivity of 80% and a specificity of 100%. 2D
tricular inflow, across both the mitral and tricuspid valves, can echo visualization of the main and proximal right and left pul-
also be used to assess for the effects of respiratory variation on monary arteries may allow visualization of an embolus lodged
ventricular fillingthe echocardiographic equivalent of pulsus in those locations. The left pulmonary artery may be difficult to
paradoxus. In the setting of tamponade, the peak LV inflow visualize as the left bronchus is frequently interposed between
velocities will decrease by more than 25% with spontaneous the TEE probe and the artery. When the PE is not extensive and
inspiration while peak RV velocities will decrease by more than easily diagnosed by echocardiography, several indirect echocar-
25% during expiration [44] (Fig. 29.6). diographic signs may suggest the presence of one. These include
evidence of acute right ventricular pressure overload with ele-
vated PA pressures, right ventricular dilation, right ventricular
Pulmonary Embolus systolic dysfunction, and increased tricuspid regurgitation. In
situations where the echocardiogram can not definitively make
Diagnosis of pulmonary embolism (PE) in ICU patients can the diagnosis of PE, the exam findings can aid the clinician in
be extremely challenging. TTE has been described as a rou- guiding therapy (Fig. 29.7).
tine screening test in patients with suspected PE. When TTE

Aortic Dissection
Aortic dissection is a life-threatening condition where an inti-
mal tear in the aortic wall allows passage of blood into a false
lumen between the intima and the media. The mortality rate
for acute aortic dissection is as high as a 1% per hour among
untreated patients in the first 48 hours [82]. A rapid and correct
diagnosis is paramount for improving survival rate. TEE has
become a standard modality for the evaluation of suspected
aortic dissection due to its availability, low cost, and noninva-
siveness [83]. In addition, TEE can be used to diagnose other
dissection-related cardiac and noncardiac complications such
as AI, coronary occlusion, pericardial effusion with or without
tamponade, and hemothorax.
Diagnosis of an ascending aortic dissection can prove to be
very challenging due to imaging-related issues. The ascending
aorta and aortic arch are areas where imaging artifacts due to
reverberation and refraction are common. These artifacts can
mimic the appearance of dissection flaps. Furthermore, at the
level of the distal ascending aorta and proximal arch, the left
FIGURE 29.6. Transthoracic subcostal view demonstrating large peri- mainstem bronchus crosses between the esophagus and aorta,
cardial effusion with end-diastolic right-ventricular chamber collapse causing image degradation. As an end result, imaging from
making the echocardiographic diagnosis of tamponade. RV, right ven- different tomographic planes and angles is mandatory to in-
tricle; LV, left ventricle. sure accurate reporting. To distinguish artifact from dissection
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282 Section II: Minimally Invasive Monitoring

FIGURE 29.8. TEE mid-esophageal four chamber view (zooming on FIGURE 29.9. TEE mid-esophageal four chamber view showing a left
the aortic valve) showing acute aortic dissection with an intimal flap to right shunt through an atrial septal defect (arrow). LA, left atrium;
(arrow). The color Doppler showing severe aortic regurgitation. RA, right atrium; ASD, atrial septal defect.

flap, the echocardiographer should establish whether or not the tension. This right-sided pressure increase may then lead to
linear echodensity conforms to the limits of the aorta or if it right-to-left shunting through the same defect. In clinical prac-
seems to disregard such anatomic boundaries as would an ar- tice, right-to-left shunt is more commonly seen in settings where
tifact. Color Doppler imaging can be used to establish whether right-sided pressure acutely increases over left-sided pressures
or not blood flow respects or ignores the echodensity. and typically involves defects in the interatrial septum. The di-
Usually, an intimal flap creates a true and false lumen. Iden- agnosis of an intracardiac shunt can be made with color flow
tification of these lumina is frequently an important goal of TEE Doppler. Typically, the flow across an atrial septal defect (ASD)
evaluation but can create a diagnostic challenge for the sonog- is of low velocity because of the small pressure difference be-
rapher. There are several indirect findings that can help differ- tween the chambers. A significant right-to-left shunt will oc-
entiate the lamina. First, the true lumen usually expands during cur when right atrial pressure exceeds LA as with severe pul-
systole and is slightly compressed during diastole [84]. Second, monary arterial hypertension. Other echocardiographic signs
spontaneous echo contrast or thrombus may be seen in the false consistent with an ASD are biatrial and RV enlargement. The
lumen as a result of stagnant flow; however, this may occasion- ratio of pulmonary to systemic blood flow, Qp /Qs , can be de-
ally be misleading as in some instances it may be the true lumen termined by Doppler flow measurements. To calculate Qp /Qs ,
where flow is stagnant. In addition, the true lumen is usually it is necessary to measure SV form the left and right sides of
smaller than the false lumen, especially in chronic dissection the heart. Transpulmonary flow, Qp, can be calculated by mea-
[85,86]. Several communications between the true and false surement of the pulmonary artery CSA and VTI at the same
lamina can often be identified by color Doppler. Although some site. Systemic flow, Qs, is calculated from the measurement of
of these communications represent entry sites allowing blood to LVOT CSA and VTI as outlined earlier (Fig. 29.9).
flow from the true to the false lumen, others are exit sites with
bidirectional flow. Identification of the starting point of a dis- CSAPA VTIPA
section can have ramifications for deciding therapy (Fig. 29.8). Qp /Qs = CSALVOT VTILVOT

ECHOCARDIOGRAPHIC ECHOCARDIOGRAPHIC
EVALUATION OF HYPOXEMIA ASSESSMENT FOR
Assessment of unexplained hypoxemia and the inability to
SOURCES OF EMBOLI
wean from ventilatory support is another potential use of Several disease processes, including intracardiac mass and
echocardiography in the ICU. Etiologies of hypoxemia that can shunt, are potential sources of systemic emboli leading to acute
be diagnosed by echocardiography include intracardiac right to vascular occlusive events. Echocardiography can be very useful
left shunting, pulmonary embolus, and LV pathologies such as in the diagnosis or exclusion of the heart as a source of systemic
LV systolic and/or diastolic dysfunction and mitral valvular ab- emboli.
normalities which can lead to pulmonary edema. The echocar- Cardiac masses: the three basic types of cardiac masses in-
diographic evaluation of pulmonary embolus and of LV and clude vegetation, thrombus, and tumor, all of which are known
mitral valvular pathologies has been discussed earlier. causes of emboli.
Intracardiac shunt is defined as an abnormal communica-
tion between two cardiac chambers and is characterized by A. Vegetation: suspected infective endocarditis is a common
blood flow across the defect [44]. The direction and volume of indication for a TEE in the ICU, since critically ill patients
flow is determined by the pressure gradient across the defect are at a high risk for bacteremia. Endocarditis is a diagnosis
and the size of the defect. A chronic left-to-right shunt may based on a combination of findings from physical exami-
lead to right-sided volume overload and, over time, right-sided nation, laboratory findings (most importantly bacteremia),
pressure overload from irreversible pulmonary arterial hyper- and echocardiographic examination. The purpose of the
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Chapter 29: Echocardiography in the Intensive Care Unit 283

echocardiographic exam is to identify valvular lesions that ically ill patients, TEE findings had therapeutic implications,
may be consistent with endocarditis, to evaluate any func- either surgical interventions or changes in medical therapy, in
tional abnormality associated with the affected valve, to 68.5% of patients. [18] 5.6% of patients underwent a surgical
assess the impact of the valvular disease on chamber func- intervention without additional investigations following their
tion and dimensions, and to discover other complications TEE. In 62.9% of patients, the TEE study had a therapeutic,
of endocarditis such as paravalvular abscess and pericardial nonsurgical impact. Included within this group was the institu-
effusion. All valves have to be carefully inspected as more tion or dose adjustment of inotropic or vasopressor drugs, an-
than one valve can be involved. Echocardiographic eval- tibiotics, anticoagulation, thrombolysis, fluid administration,
uation of valvular endocarditis involves multiple acoustic and the initiation of advanced hemodynamic monitoring. This
windows and 2D views, since the vegetation may be seen represents the largest reported series evaluating the use of TEE
only in a certain tomographic planes. Most commonly, the in a noncardiac surgical ICU setting.
vegetation is attached to the upstream, lower pressure side The current body of literature that focuses on the use of
of the valve leaflet. It appears as an abnormal, echogenic, echocardiography in the ICU lacks prospective, randomized
irregular mass attached to a leaflet [44]. Although vegeta- controlled studies demonstrating efficacy in decreasing mor-
tions can be attached to any part of the leaflet, attachment bidity and mortality and cost-effectiveness. However, this lit-
to the coaptation point is most common. erature does point to the potential benefits that may be gained
B. Thrombus: Intracardiac thrombi form in areas of blood by the availability of echocardiography in ICUs. It also demon-
stasis or low flow. Examples of this within the ventricles strates the potential benefit of more widespread and advanced
include ventricular aneurysm, pseudoaneurysm, and areas training in echocardiography for intensive care physicians.
adjacent to severely hypokinetic or akinetic wall segments.
LA thrombi are usually associated with atrial enlargement,
mitral stenosis, and atrial fibrillation. Most LA thrombi are
found in the LA appendage, which is best visualized by TEE.
Thrombi are usually more echogenic than the underlying
FUTURE POTENTIAL USE OF
myocardium and have a shape distinct from the endocar- ECHOCARDIOGRAPHY IN
dial border. Imaging from several tomographic planes is TRAUMA PATIENTS IN THE ICU
frequently necessary to rule out artifact that may mimic
thrombus. Again, color Doppler can be used to establish Recently, hand-carried ultrasound (HCU) devices have been in-
whether or not blood flow respects the apparent bound- troduced into clinical use [8789]. These devices are attractive
aries of the suspected thrombus to attempt to distinguish it because of their size, portability, and cost. They may be easily
from an echo artifact. stored in the ICU, which makes them immediately available for
C. Cardiac Tumors: Nonprimary tumors, which are about bedside use. Portable echocardiograms performed at the bed-
twenty times more common than primary cardiac tumors, side can help the physician to diagnose and manage critically
can involve the heart by either metastatic or lymphatic ill patients. Although overall image and color flow qualities
spread, or invasion from neighboring malignancies. They of hand-carried echocardiographic devices are not equivalent
can invade all structures of the heart; the pericardium, epi- to the standard full-featured machines, they have been found
cardium, myocardium and endocardium. About 75% of to compare well with standard platforms for the identification
metastatic cardiac tumors involve the pericardium and epi- of cardiac pathology [90]. Reports in the literature regarding
cardium and most commonly present as pericardial effu- the use of these devices are mixed. Early reports showed favor-
sion. A definite diagnosis usually cannot be made from the able results in the outpatient setting [88], when used on hos-
echocardiographic images alone. A probable diagnosis can pital rounds [89], and in a small cohort of ICU patients [87].
sometimes be made by incorporating the clinical informa- Some of these reports have shown a good correlation between
tion along with the echocardiographic images. Renal cell these devices and standard echocardiographic equipment for
carcinoma has a propensity to develop finger-like projec- the evaluation of wall motion abnormalities and valvular re-
tions that may extend up the IVC into the right atrium. Oc- gurgitation. [91,92] In addition, data from a few studies have
casionally, uterine tumors may present in a similar manner shown a high level of agreement between hand-carried de-
D. Shunts: As described earlier, right-to-left shunting can play vice examination and standard echocardiographic examination
a role in hypoxemia. In addition, any right to left commu- [87,89,9395]. In one study, examination with a HCU device
nications can allow for paradoxical emboli to travel from was able to evaluate and answer 85% of clinical questions
the systemic venous to arterial circulation. This can lead to presented by the referring physician. Of those questions, 86%
stroke or vascular occlusive disease of one or several organs. were later confirmed as correctly answered [96]. Although one
study has demonstrated the relative equivalence of the HCU
device with regards to 2D imaging, even in mechanically venti-
IMPACT OF ICU lated patients [97], other studies have shown it to be inferior to
standard echocardiography when comparing spectral Doppler
ECHOCARDIOGRAPHY ON capabilities [98]. Other reports have shown that HCU imaging
PATIENT MANAGEMENT may lead to inadequate evaluation of pulmonary hypertension,
valvular disease, and LV outflow tract obstruction in severely ill
Indications for performing a TEE study vary significantly de- patients [96,97]. In ICU cohorts, several reports have demon-
pending on patient type: for patients in the medical and neuro- strated similar shortcomings. [96,98]
surgical ICUs, most TEE studies are performed to rule out or In addition to cardiac evaluation, the HCU can be used in
confirm bacterial endocarditis (medical ICU) and/or a cardiac the ICU to aid in placing central venous catheters and arterial
source of emboli (neurosurgical ICU). In contrast, in medical- lines as well as for ultrasound guidance of pleurocentesis and
surgical and coronary ICU patients the most common indica- paracentesis. The day when the HCU becomes an extension
tions are for diagnosing aortic dissection, valvular dysfunction, of the traditional physical exam may not be far off. It is also
or hemodynamic instability [18]. not unreasonable to imagine the HCU used by the hospital
A recent review of 21 studies evaluating the impact of TEE code team for better diagnosis and patient management during
on patient management demonstrated that out of 2,508 crit- resuscitative efforts.
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284 Section II: Minimally Invasive Monitoring

field will potentially improve the imaging quality and clini-


CONCLUSION cal capabilities and allow for implementation of this tool in
new situations and settings. With this in mind, proper edu-
Echocardiography is an important tool for diagnosis and mon- cation and implementation of utilization guidelines becomes
itoring of the critically ill. With time, utilization of echocar- increasingly important. To achieve optimal clinical results, clin-
diography is likely to become even more widespread. It is icians must be well aware of the limitation as well as the
quickly establishing itself as a highly efficient and reliable benefits of each modality and when and how they should be
clinical tool. The echo examination can be performed in nu- used. An important step toward achieving this will be inclu-
merous clinical settings and in a diverse patient population, sion of echocardiographic training within critical care fellow-
including the most complex. Technical advancements in this ships.

References
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2. Daniel WE, Erbel R, Kasper W, et al: Safety of transesophageal echocardio- J Am Coll Cardiol 22:14941500, 1993.
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P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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286 Section II: Minimally Invasive Monitoring

CHAPTER 30 MONITORING
GASTROINTESTINAL TRACT FUNCTION
RUBEN J. AZOCAR, LAURA SANTOS PAVIA AND SURESH AGARWAL

Gastrointestinal system function is of paramount importance sessed to evaluate feeding tolerance and prevent nosocomial
for the maintenance of the bodys homeostasis, which is not pneumonias.
only limited to the important functions of digestion and ab- Traditionally this is done by quantification of gastric resid-
sorption but also closely related to immune function. Monitor- ual volumes (GRV), which despite being easy to perform, are
ing the gastrointestinal tract function remains largely based on a poor predictor of the patients ability to tolerate enteral nu-
clinical exam and a few diagnostic tests. The majority of the trition. In addition, a recent article suggests that the use of
tests that are available have been primarily used for research residual volumes as a marker of risk for aspiration in critically
purposes and are not available at the bedside of the critically ill patients has poor validity [3].
ill patient (Table 30.1). Reflectometry (RFT) of gastric contents seems to provide
This chapter examines the diagnostic modalities available, complementary information on the adequacy of gastric empty-
on an organ system basis, for assessing abnormalities in the ing [4] by differentiating gastric contents from feeding formula
critically ill patient. when measuring GRVs. This model implies the measurement
of the Brix value (BV) of the gastric aspirate at several time
points. The BV is the refractive index of a substance, which is
ESOPHAGUS the degree of deviation or refraction of a beam of light when
passing obliquely through a solution [5]. Chang et al. [6] stud-
Tests of Esophageal Motility and Lower ied 36 patients receiving continuous enteral nutrition. Based
on the data collected, the authors created and algorithm using
Esophageal Sphincter Function BVs and GRV, which suggest values at which enteral feedings
can be safety continued. RFT uses an inexpensive handheld in-
Impaired tubular esophageal motility is involved in the patho- strument (refractometer) similar to a small telescope. A drop of
genesis of gastroesophageal reflux disease (GERD) which might the solution is placed in the viewing window and the BV is read
cause nosocomial pneumonias in the critically ill. thought the eyepiece. The use of RFT is simple, inexpensive,
Esophageal manometry has been used extensively to study and quick, but it has not been compared with what is consider
GERD in critically ill patients. One study, of 15 critically ill the gold standard, gamma scintigraphy.
patients, demonstrated that low esophageal sphincter (LES) Gamma scintigraphy is a quantitative method to measuring
pressure (mean 2.2 0.4 mm Hg) and poor motor response gastric motility by administering radiolabeled solid food (usu-
to reflux correlated with the presence of GERD. Further- ally greater than 200 kcal) and measuring transit after 2 to
more, low LES pressures were associated with frequent reflux 4 hours. The administration of liquids may not be relevant as
episodes (60% of untreated patients) and decreased esophageal liquids may empty from the stomach even as solid food remains
motility [1]. behind. The feasibility of scintigraphy testing for the critically
In a more recent 24-hour manometric study, the authors ill patient makes is difficult as it is often impractical to trans-
demonstrated that propulsive esophageal motility is impaired port these individuals to the nuclear radiology suite for this
in critically ill patients receiving sedation and postulated that study.
24-hour motility studies appear to be a valuable and feasible Breath tests are a novel and useful bedside technique to as-
method to analyze and quantify esophageal motor disorders in sess gastric emptying of both solids and liquids by using 13 C-
critically ill patients [2]. or 14 C-labeled octanoic acid. The absorption of the labeled oc-
Twenty-fourhour pH and impedance monitoring further tanoic acid in the small intestine and subsequent metabolism
elucidates the function of the LES and the amount of gastric in the liver produce 13 CO2 , which can be measured in the ex-
reflux a patient is experiencing. Over a 24-hour period, the pH haled air. The delivery of the 13-octanoic acid into the duo-
should not drop below 4 frequently or for a prolonged duration denum is the rate-limiting step for these processes. As such,
(6% of total time in the supine patient, 10% of total time in measurement of 13 CO2 levels correlates with the rate of gas-
the upright patient). tric emptying. Ritz et al. [7] founded that gastric emptying of
Both barium swallow and real-time fluoroscopy yield func- a caloric-dense liquid meal is slow in 40 to 45 of unselected
tional and anatomic data about the esophagus and the swal- mechanically ventilated patients by using the 13-octanoic acid
lowing mechanisms. Similarly, an isotope swallow, using a breath test. They concluded that this test is a useful bedside
technetium-99 colloid and a gamma camera, may provide data adjunct to measure gastric emptying in ventilated, critically ill
regarding esophageal physiology. patients.
Gastroduodenal manometry has also been used to study
STOMACH the effects of critical illness in gastric motor activity. Nguyen
demonstrated that in critical illness in addition to impaired
proximal and distal gastric motor activity, the association be-
Tests of Gastric and Duodenal Motility tween the two regions was also abnormal which interferes with
meal distribution and affects GE [8]. Similar data was observed
Delayed gastric emptying (GE) is common during critical ill- by Chapman et al. who noted that in critical illness there is
ness. Patients receiving enteral nutrition are frequently as- slower GE probably associated by fewer anterograde waves
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 30: Monitoring Gastrointestinal Tract Function 287

TA B L E 3 0 . 1
TESTS FOR MONITORING GASTROINTESTINAL FUNCTION

Organ Function Test

Esophagus Motility/LES function Barium swallow


Isotope swallow
Esophageal manometry
Esophageal pH and impedance
Stomach Motility Gastric residuals
Refractometry
Gastroduodenal manometry
Breath tests
Acetaminophen absorption test
Mucosal permeability and Gastric tonometry
ischemia Laser Doppler flowmetry
Near-infrared spectrometry
Positron emission tomography
Microdialysis
Orthogonal polarization spectrometry
Sidestream Dark Field
Small intestine Absorption Stool analysis: fecal pH, fecal osmotic gap,
steatorrhea
Carbohydrates absorption tests (d-xylose,
l-rhamnose)
Acetaminophen absorption test
Breath tests
Pancreas Exocrine functions Fecal fat concentration
Amylase/lipase
Secretin tests
Liver Liver function test Static tests
Transaminases
Bilirubin
Albumin
Lactate
Coagulation tests
Dynamic test
MEGX
ICG
Breath tests
Hepatic blood flow tests ICG
MEGX
Cholestasis Transaminases
Bilirubin
Alkaline phosphatase
Gamma glutamyl transpeptidase
Ultrasound
HIDA

HIDA, hepatic iminodiacetic acid; ICG, indocyanine green; LES, low esophageal sphincter; MEGX,
monoethylglycinexylidide.

and more retrograde waves as recorded when measuring the sess GE, which has not allowed standardization or validation
antroduodenal motility [9]. despite its obvious benefits of availability, lack of radiation and
The acetaminophen absorption test may also be used good interobserver agreement. GIM, which measures increases
to assess gastric emptying, by administering 1,000 mg of in impedance as the stomach fills, and declines as it empties,
acetaminophen and measuring serum concentrations of ac- seems to be a promising tool. However, the time needed to com-
etaminophen over a 1-hour period to construct an area under plete and the requirement of a fasting state for baseline may
the curve (AUC) absorption model. This AUC is then compared interfere with its use in the clinical setting.
to a known AUC model constructed from healthy volunteers.
The utility of this test may be quite variable in the critically
ill patient given differences in volume of distribution, hepatic Tests of Mucosal Permeability and Ischemia
metabolism, and renal clearance [5].
Other novel methods to assess GE include the use of ultra- Microcirculatory dysfunction plays an important role in the
sound and gastric impedance monitoring (GIM). Ultrasound pathogenesis of the systemic inflammatory response, sepsis,
has used different equipment and different methods to as- and shock. Global hemodynamic measurements do not assess
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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288 Section II: Minimally Invasive Monitoring

oxygen delivery at the microcirculatory level. Gut ischemia at showed that NIRS gut pH correlated with the pH obtained by
this level causes changes in permeability leading to bacterial microelectrodes. This technology has progressed to the mea-
translocation that may initiate, perpetuate, and aggravate sep- surement of muscle tissue oxygenation and microcirculation by
sis and multisystem organ failure (MOF). Many methods have measuring thenar muscle oxygenation saturation with promis-
been used to study the gut microcirculation. Unfortunately, ing results [23].
most of them have failed to be applicable in the clinical set-
ting or have flaws in the data collected.

Tonometry POSITRON EMISSION


Although the diagnosis of bowel ischemia may be done by a
TOMOGRAPHY
variety of different methods, gastric tonometry is the simplest, Positron emission tomography may also be used to evaluate re-
most practical, and least invasive [10]. It attempts to deter- gional blood flow. Fluoromisonidazole accumulation has been
mine the perfusion status of the gastric mucosa by measuring used to demonstrate abdominal splanchnic perfusion and re-
the local PCO2 [11]. As perfusion to the stomach decreases, the gional oxygenation of the liver in pigs; however, the lack of
PCO2 in the tonometer will increase. Once cellular anaerobic portability of this technique makes it difficult to use for moni-
respiration starts, the hydrogen ions titrate with bicarbonate, toring in the intensive care unit (ICU) [14].
with the end result of more CO2 production by mass action. By
estimating the PCO2 gap (the difference between gastric mu-
cosa and arterial CO2 ) the gastric perfusion can be assessed
[12]. Unfortunately, the use of the technique has not gained MICRODIALYSIS
widespread popularity despite many clinical studies that have
validated gastric tonometry as a valuable and easily accessible Microdialysis measurement of mucosal lactate is a novel way
prognostic tool [13,14]. This may be explained by the possibil- to assess gut mucosal ischemia. Tenhunen et al. [24] inserted
ity of error in the determination of the PCO2 and interoperator microdialysis catheters into the lumen of the jejunum, the je-
variability [15,16]. Other pitfalls include multiple local effects, junal wall, and the mesenteric artery and vein of pigs. Subse-
including increased gastric secretions and refluxed duodenal quently, the animals were subjected to nonischemic hyperlac-
contents; both of which can increase CO2 measurement and tataemia or an episode of mesenteric ischemia and reperfusion.
lead to false PCO2 measurement, and that this technique may The lactate levels from the jejunal wall and the jejunal lumen
only represent one region of perfusion [11]. were compared. The gut wall lactate was increased in both the
Recently, the measurement of carbon dioxide in the sub- nonischemic and the ischemic lactataemia whereas the lactate
lingual mucosa by sublingual capnometry has been advocated measured from the jejunal lumen only was altered significantly
as a monitor for tissue oxygenation and as an end-point for during true ischemia.
resuscitation [17]. Studies have demonstrated a good correla- Microdialysates of other substances have also been mea-
tion between gastric mucosal and sublingual mucosa PCO2 . In sured, including glucose and glycerol, showing that, while lac-
addition, sublingual mucosa PCO2 seems to respond faster to tate levels increase with ischemia, intestinal wall glucose levels
therapeutic interventions [18]. drop with the same stressor. Glycerol was increased, but the
changes were seen later than the changes in lactate [25]. Sim-
Laser Doppler Flowmetry ilarly, increases in the lactate/pyruvate ratio in both intraperi-
toneal or intraluminal placed microdialysis catheters have
Laser Doppler flowmetry (LDP), which estimates gastric and je- correlated with hypoperfusion [26]. As glucose from the
junal blood perfusion by integrating red blood cell content and splanchnic circulation is inhibited, pyruvate accumulates in the
velocity, correlates well with absolute blood flow. The flowme- tissue and, in the setting of inadequate oxygen delivery, is bro-
ter consists of a laser source, a fiberoptic probe, and a photode- ken down to lactate. Using glycerol as a marker, Sollingard et
tector with a signal-processing unit. The laser conducts through al. [27] suggested that gut luminal microdialysis could serve as
the tissue by a flexible fiberoptic guide. The probe contains an a valuable tool for surveillance not only during ischemia, but
optic fiber for transmission of laser light to the tissue and two also after the ischemic insult. This group has also suggested
fibers for collecting the reflected scattered light. The signal- that gut luminal lactate measured by this technique correlates
processing unit consists of a photodetector and an analog cir- well with changes in the permeability of the intestinal mucosa
cuit to analyze the frequency spectrum of the scattered light. after ischemia [28].
By determining the instantaneous mean Doppler frequency and The assessment of the barrier function using colon submu-
the fraction of backscattered light that is Doppler shifted, the cosal microdialysis with a radioactive tracer substance has also
signal-processing unit provides a continuous output propor- been reported. No data comparing these results with local tis-
tional to the number of red blood cells moving in the measur- sue chemistry have been reported [29].
ing volume and the mean velocity of these cells. Measurements These data support the idea that microdialysis could be a po-
are considered satisfactory if (a) the measurement is stable for tentially useful method to monitor gut ischemia. However, even
15 seconds; (b) the measurement is free of motion artifacts; under investigational conditions, technical difficulties were re-
(c) pulse waves can be clearly identified; and (d) the reading is ported in up to 15% of cases by either damage to the mi-
reproducible. Although LDP is relatively easy to use and it is crodialysate membrane, dislocation of the probe, or incorrect
noninvasive, it does not account for blood flow heterogeneity, placement [30].
a major parameter of microcirculation [19].

Near-Infrared Spectometry
ORTHOGONAL POLARIZATION
Near-infrared spectrometry (NIRS) has been used to measure
local tissue blood flow and oxygenation at the cellular level SPECTROMETRY AND
[20]. Local oxygen delivery and oxygen saturation can be de- SIDESTREAM DARK FIELD
termined by comparing the differences in the absorption spec-
trum of oxyhemoglobin with its deoxygenated counterpart, de- Recently devices able to allow the microcirculation to be vi-
oxyhemoglobin [21]. Puyana et al. [22] reported using NIRS sualized directly have been used clinically [31]. Orthogonal
to measure tissue pH in a model of experimental shock and polarization spectrometry (OPS) and the sidestream dark field
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Chapter 30: Monitoring Gastrointestinal Tract Function 289

provide high-contrast images of the microvasculature. Both de- absorbed in the small intestine by a passive mechanism. The
vices are based on the principle that green light penetrates a test consists in the ingestion of a 25 g dose of d-xylose and the
tissue and that then green light is absorbed by red blood cells subsequent measurement of the levels in the serum or urine. In
(RBCs) hemoglobin contained in superficial vessels. Therefore, normal individuals, a serum sample taken 1 to 2 hours after
capillaries and venules can be visualized if they contain RBCs. ingestion will reveal a level of 25 mg per dL and a 5-hour urine
The easiest assessment method is the microvascular flow index. collection will result in at least 4 g of this substance. Many enti-
The image is divided into four quadrants and the flow is char- ties such celiac disease, alterations in gastrointestinal motility,
acterized and scored as absent (0), intermittent (1), sluggish (2), and impaired function of the pylorus will result in abnormal
or normal (3). The values of the quadrants are then averaged. results. In the critically ill, renal function may be altered and
Clinical studies suggest that this is a good method to assess mi- may alter the results of the urine test. Chiolero et al. [39] stud-
crocirculation in critically ill patients. Those patients with more ied the intestinal absorption of d-xylose in critically ill patients
severe alterations have a higher mortality and that if these alter- that were tolerating enteral feeding. They introduced d-xylose
ations persist they may lead to MOF [3234]. In most studies, to the stomach or the jejunum and found that although the
the sublingual circulation has been the site chosen. An attempt levels in plasma in all patients in the study increased indicating
to use this method for gut ischemia by assessment of the villi proper gastric emptying, in those receiving the compound in the
microvasculature per se was not successful. Likely causes in- stomach, the levels of d-xylose were lower than normal, indi-
clude blood flow redistribution, heterogenicity of the intestine cating delays or depression in absorption. These results were
microcirculation, and suboptimal OPS imaging, which resulted similar to a prior study in trauma and septic patients. In that
in large interobserver differences in the quantification of vessel study, in both groups the d-xylose test showed abnormal results
density [35]. at the onset of the illness with resolution by 1 to 3 weeks after
trauma or resolution of sepsis. Interestingly, enteral feedings
were tolerated by these patients before the test results returned
SMALL INTESTINE to normal [40]. As the patients in both studies were tolerating
tube feeds even with abnormal d-xylose test results, Chiolero
et al. [39] suggested that this test may not be a good indicator
Tests of Intestinal Absorption to determine the capacity of patients to tolerate enteral feeds.
This does confirm that absorption of d-xylose stays depressed
Clinically, the recognition of malabsorption in the ICU is as- for a prolonged period of time in the critically ill.
sociated with a variety of signs and symptoms. On physical Johnson et al. [41] also found decreased absorption in the
exam, abdominal distention, abdominal pain, and increased septic population when compared with healthy individuals.
flatulence may be present. Isolated carbohydrate malabsorp- They used an oral test solution that contained 5 g of lactu-
tion may result in increased gas production, which can lead to lose, 1 g of l-rhamnose, 0.5 g of d-xylose, and 0.2 g of 3-O-
flatulence, bloating, and abdominal distention. Likewise, diar- methyl-d-glucose. l-rhamnose is absorbed by passive diffusion
rhea may indicate a problem with absorption of nutrients, but and therefore particularly sensitive to changes of the absorp-
again it is nonspecific and other potential causes should be ex- tive capacity of the gut when compared with d-xylose and 3-
amined. Steatorrhea may indicate pancreatic insufficiency. It is O-methyl-d-glucose, which depend on specific carrier mech-
also important to elicit the past medical history since it can pro- anisms. The authors found that septic patients had decreased
vide useful information in regards to primary (i.e., lactose intol- l-rhamnose/3-O-methyl-d-glucose ratios when compared with
erance) or secondary (i.e., chronic pancreatitis) malabsorptive normal individuals, a result consistent with decrease absorptive
problems. capacity during sepsis. They also used the lactulose/l-rhamnose
Malabsorption can be detected by a variety of tests. Stool ratio to assess permeability of the gut. This group concluded
analysis may provide information regarding carbohydrate and that the changes in the absorptive capacities of the gut may
fat malabsorption. Bacterial fermentation of malabsorbed car- contribute to the pathophysiology of sepsis.
bohydrates may result in an acidic fecal pH. Eherer and Ford-
tran [36] found that when diarrhea was caused by carbohydrate
malabsorption (lactulose or sorbitol), the fecal fluid pH was al- Other Tests
ways less than 5.6 and usually less than 5.3. Other causes of
The rapid absorption of acetaminophen at the jejunal level can
diarrhea rarely caused fecal pH to be as low as 5.6 and never
also aid the assessment of the absorptive capacity of the gut.
caused a pH less than 5.3.
It has, however, been used more to assess gastric emptying [5]
Another measurement is of fecal osmolarity. Assuming the
and tube feeding location for enteral feeding [42]. From these
fecal osmolality is similar to that of the serum, the fecal os-
data, it appears that either carbohydrate absorption tests or the
motic gap can be calculated. A sample is taken from the stool
acetaminophen test could be used to a monitor absorption in
supernatant and if the value is greater than 50 to 100 mOsm,
the critically ill. No correlation has been established between
it would suggest the presence of an unmeasured solute. Al-
tolerating tube feeds and the degree of absorption. The role of
though this solute may be a malabsorbed carbohydrate, other
this test may be to monitor improvement of absorptive function
compounds, such as sorbitol, or ions, such as sulfates, may
of the gastrointestinal tract after critical illness.
yield similar results.
Breath tests are a simple and safe alternative to diag-
Steatorrhea is defined as the presence of at least 7 g of fat
nose many gastrointestinal conditions including malabsorp-
in a 24-hour stool collection [37]. Sudan II stain is a simple
tion. Most of the data are from the gastroenterology literature
screen testing and it is helpful to detect those patients with
and are used to diagnose specific gastrointestinal pathologies.
mild degrees of steatorrhea (7 to 20 g per 24 hours). The gold
However, it seems feasible to apply this test to the critically
standard is represented by quantitative fecal fat analysis [38].
ill population. These tests are based on the appearance of a
Stool is collected over 2 to 3 days while the patient ingests 75
metabolite of a specific test substance in the breath [43]. Both
to 100 g of fat within 24 hours. Normal values are less than
hydrogen gas excretion and carbon dioxide appearance on
7 g per day. However, this test is laborious and may not help
breath tests are available.
with differentiating diagnoses.
If carbohydrates are not absorbed in the small intestine,
they are fermented in the colon by colonic bacteria. This pro-
D-Xylose Uptake cess results in the production of hydrogen. For example, in
The d-xylose test has been used in the diagnosis of malabsorp- cases of lactose intolerance, this disaccharide will reach the
tion. This pentose sugar of vegetable origin is incompletely colon and a peak on the end-expiratory hydrogen of more of
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290 Section II: Minimally Invasive Monitoring

20 ppm over baseline by either gas chromatography or portable ity of injury, they do indicate that injury is present. Pancreatitis
hydrogen analyzers at 2 to 3 hours indicates malabsorption for will be covered in other portions of this text (see Chapter 99).
this carbohydrate [44]. A similar test using a nonabsorbable
carbohydrate, such as lactulose, has been used for the diag- Secretin Test
nosis of bacterial overgrowth in which the peak of hydrogen
occurs earlier but is less pronounced. The use of carbon diox- The secretin test is a direct measurement of pancreatic exocrine
ide that results from the fermentation of labeled substances has function that measures the intraduodenal secretion of bicar-
also been reported. The use of both radioactive 14 C and stable bonate, amylase, and trypsin after exogenous administration of
13
C compounds has been described. However, since the nonra- secretin. Generally, bicarbonate and amylase secretion will in-
dioactive substances can be detected by mass spectrometry and crease in adults, whereas the increase of bicarbonate, amylase,
do not involve radiation exposure, they seem to be preferred and trypsin will increase in children. In the presence of chronic
over the radioactive ones [45]. pancreatitis, concentrations and quantity will be diminished;
In critically ill patients 13 C-acetate has been studied to eval- in contrast to pancreatic cancer, which presents with dimin-
uate intestinal absorption [12]. Acetate possesses interesting ished volume but normal concentration. The maintenance of
properties that allow its use for absorption purposes since it is normal concentrations in pancreatic cancer is attributed to nor-
readily absorbed by the intestinal mucosa and it is metabolized mal pancreatic function in the nonmalignant portions of the
through oxidative metabolism by nearly all body tissues. Ac- pancreas.
etate is converted into acetylCoA and then oxidized to CO2 .
When marked acetate is provided, the 13 CO2 is then measured
in the breath by mass spectometry. 13 C-acetate was provided LIVER
by intravenous infusion and enterally at both gastric and je-
junal levels. Surprisingly, the kinetics of all three routes was Liver function includes vital functions of metabolism, synthe-
similar (the gastric group was delayed but probably secondary sis, detoxification, and excretion. It is then, not surprising that
to the time for gastric emptying), indicating a rapid absorption patients with deteriorating liver function will have a more com-
and metabolism. The authors concluded that further studies plex course during critical illness. Traditionally, tests related to
are needed in this area before this particular breath test can measuring the products of liver synthesis have been use to as-
be used to assess tolerance of enteral feeding [15]. C-octanoic sess liver function and damage in a static fashion, but as it will
acid has been used to assess gastric emptying in the critically ill be discussed, tests that evaluate the liver function in a more
and was discussed in the motility section [3]. Other breath tests dynamic fashion are also available.
have been use to assess absorption anomalies [44]. In the case
of bile acid malabsorption and bacterial overgrowth, cholyl-
glycine (glycocholic acid) is not absorbed at the ileum and the
glycine is cleaved from the labeled cholylglycine by colonic bac- Tests of Liver Injury and Static Function
teria. Glycine is then absorbed and metabolized into CO2 . The
In the critically ill, different levels of dysfunction can be man-
CO2 can be detected in the breath and 4.5% of the radioactivity
ifest ranging from mild elevation of the transaminases to pro-
is seen in the breath over the subsequent 6 hours. To differenti-
found hepatic failure. It is difficult to separate completely those
ate between bacterial overgrowth and bile acid malabsorption
tests that assess liver injury from those that are related to its
a stool collection is needed to detect bile acid losses.
function as some will suggest the insult to the organ as well
In pancreatic insufficiency mixed triglycerides that are hy-
as the alteration on its function, particularly in the acute set-
drolyzed to glycerol and fatty acid are then absorbed and finally
ting. The tests described in this section are considered static
metabolized in the liver where they release labeled CO2 . This
and will reflect an injury that has occurred and changes on
test indirectly measures intraluminal fat digestion by pancreatic
the livers function, but they do not assess current functional-
enzymes. Other substances such as triolein, hiolein, tripalmitin,
ity, particularly in the patient with chronic liver failure. How-
and labeled starch have been use for this purpose but are not
ever, in a critically ill patient with no prior liver problems these
sensitive enough for patients with mild disease [44].
tests are helpful in detecting an ongoing morbid process in the
liver.

PANCREAS Transaminases
Although the pancreas performs both endocrine and exocrine Serum glutamic-oxaloacetic transaminase (SGOT), or aspar-
functions, only the functions affecting the digestive tract are tate aminotransferase (AST), and serum glutamate-pyruvate
discussed here. Although diabetes mellitus may decrease gastric transaminase (SGPT), or alanine aminotransferase (ALT), are
motility, the diagnosis and management of endocrine disorders enzymes that are present in all organism cells; however, they
will be dealt with elsewhere (see Section VIII). are found in highest concentration in the hepatocyte: SGPT in
the cytoplasm and SGOT in the cytoplasm as well as the mito-
chondria. Therefore, as injury and necrosis of the hepatocyte
occurs the enzymes levels in the plasma will increase reflecting
Fecal Fat Concentration the damage to this organ. The rate and the level of the eleva-
tion are usually related to the onset of the dysfunction and its
As discussed in the digestion and absorption section, in the severity. Severe ischemic hepatitis is characterized by an acute
presence of pancreatic steatorrhea, fecal fat concentration is elevation of the aminotransferases to at least 20 times the upper
elevated [37,38]. Diarrhea resolves and fecal fat concentration limit of normal [45].
abates once the individual is challenged with enzyme replace-
ment therapy.
Bilirubin
One of the main functions of the liver is to conjugate and ex-
Amylase/Lipase crete bilirubin, a product of erythrocyte breakdown. Therefore,
These simple blood tests are elevated in the presence of acute either elevations of the bilirubin clinically (jaundice, icterus,
pancreatic inflammation. Although not indicative of the sever- dark urine) or by laboratory testing should raise the clinical
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Chapter 30: Monitoring Gastrointestinal Tract Function 291

suspicion of liver dysfunction or injury. It is possible to deter- quantitative tests may be more complicated to perform and
mine if the bilirubin has already been conjugated, and this helps more expensive than conventional tests, they may prove supe-
in searching for the causes of the hyperbilirubinemia. Uncon- rior in monitoring the degree of liver dysfunction by monitoring
jugated (or indirect) hyperbilirubinemia is the result of excess the livers metabolic or clearance functions [47]. Different tests
production of bilirubin (e.g., hemolysis) or decreased hepatic have been used in an attempt to have a dynamic or real-time
uptake. Conjugated hyperbilirubinemia results when intrinsic assessment of the livers metabolic or clearance functions and
parenchymal injury or biliary obstruction exists. Acute changes complement the information provided by the static tests.
of the conjugated bilirubin levels are related to acute hepatocyte
injury in situations such as viral hepatitis or ischemic hepatitis Monoethylglycinexylidide
and will be related to the increase in the transaminases. This
The hepatic metabolism of lidocaine by sequential oxidative
should alert the clinician of injury and dysfunction of the liver.
N-dealkylation by the cytochrome P450 system into its major
Tests to study cholestasis are described in a separate section
metabolite; monoethylglycinexylidide (MEGX) is a dynamic
of this chapter. However, it should be remembered that biliary
liver function test [48]. Because of the high extraction ratio of
obstruction may also lead to hepatic dysfunction.
lidocaine by the liver, this test not only evaluates liver metabolic
capacity but also hepatic blood flow [49]. Detection of this
Lactate metabolite can be accomplished by different techniques such
The ability of the liver to clear lactate is profound. Greater than as immunoassay based on the fluorescence polarization im-
99% of lactate is cleared by first pass metabolism by a healthy munoassay technique, high performance liquid chromatogra-
liver. Inability to clear lactate may be an indicator of poor or- phy, and gas liquid chromatography [49]. Fluorescence polar-
gan perfusion and anaerobic metabolism, and this metabolite ization immunoassay technique may cross react with another
can be used as a resuscitation parameter. If other indicators metabolite (3-OH-MEGX). The other two tests are specific for
of resuscitation are optimized and the arterial lactate levels re- MEGX.
main elevated, this may indicate severe liver dysfunction and This test has been useful in patients with end-stage liver dis-
injury, particularly in patients in shock. ease in which a MEGX level at 15 or 30 minutes of less than
10 mg per L indicates poor 1-year survival. In liver transplant
recipients, a change in the levels may indicate a deterioration
Albumin of the graft function. In critically ill patients, a rapid decrease
Liver function may also be evaluated by measuring its ability to in MEGX test values have been associated not only with liver
synthesize a variety of proteins. Albumin is the most common dysfunction but with the development of multisystem organ
protein measured when evaluating liver synthetic ability. Al- failure and an enhanced systemic inflammatory response [49].
though hepatocellular dysfunction may be the cause of hypoal- McKindley et al. [50] reported on the pharmacokinetics of li-
buminemia, the protein concentration also varies in a variety of docaine and MEGX in a rat model of endotoxic shock. They
diseases/acute injury phases (e.g., burns, nephrotic syndrome, found that the metabolism of both compounds was altered and
etc.) and can be nonspecific. It is a better marker to assess the attributed the results to both the reduced hepatic blood flow
degree of chronic hepatic failure than acute dysfunction and it and altered function of the cytochrome P450 system, particu-
does not reflect injury. larly cytochrome P4503A4. Chandel et al. [51] also report the
use of this test in an animal model of hypovolemic shock. They
found that the MEGX levels were significantly lower in shocked
Coagulation Studies animals. Once the animals were resuscitated with Ringers lac-
More sensitive and specific measurements of hepatic function tate, the MEGX levels were higher but still lower than the con-
include evaluation of the coagulation cascade and the produc- trol group. They concluded that shock produced significant
tion of specific coagulation factors. If the prothrombin time depression of hepatocyte function and that MEGX seemed a
(PT) is elevated, one of two conditions exists: vitamin K de- suitable tool for clinical evaluation and therapeutic interven-
ficiency or deficiency in vitamin K dependent factors (II, VII, tion after shock.
IX, and X). If vitamin K has been replaced and the PT remains
elevated, this is very specific for liver dysfunction. This is not Dyes
a sensitive test, as the PT remains normal as long as 20% of Another dynamic test of liver function is related to the rate
the liver remains intact. Far more sensitive, although more time of elimination of dyes such as indocyanine green (ICG) and/or
consuming and costly, is the measurement of factor V levels. bromsulphthalein [52]. Most of the data in the critically ill
Factor V, produced in the liver, is not vitamin K dependent, come from the use of ICG. This dye is a water-soluble inert
and its deficiency is both sensitive and specific for hepatocellu- compound that is injected intravenously. In the plasma, it binds
lar synthetic dysfunction. to albumin and is then selectively taken up by hepatocytes. The
ICG is then excreted into the bile via an adenosine triphosphate
(ATP)-dependent transport process. This compound is not me-
Dynamic or Qualitative tabolized and does not undergo enterohepatic recirculation.
Tests of Liver Function The excretion rate of ICG into the bile reflects the hepatic ex-
cretory function and the hepatic energy status and justifies its
Although the tests discussed in the earlier section are very im- use as a tool for assessment of liver function [53]. In a study
portant in detecting and helping the clinician assess liver dys- comparing cirrhotic and noncirrhotic patients, Hashimoto and
function, they are not perfect as some are nonspecific (lactate, Watanabe [54] found that ICG clearance was proportional to
coagulation disorders, albumin levels) or reflect past damage liver parenchymal cell volume and is related to the hepatic dys-
(transaminases) in assessing the current state of liver function- function in cirrhotic patients. Traditionally, the ICG clearance
ality. Figg et al. [46] compared the Pughs classification, which has been measured by a series of blood samples and subsequent
is based in clinical and laboratory data, with dynamic or qual- laboratory analysis. NIRS has also been used to measure hep-
itative methods of hepatic function and found that the Pughs atic ICG clearance with promising results in the assessment of
classification seemed to be a reliable indicator of the degree of hepatic parenchymal dysfunction [55].
chronic liver disease but could not replace qualitative metabolic Fortunately, bedside techniques have become available
markers particularly isozyme-specific markers. Although the to measure the plasma disappearance rate (PDR) of ICG.
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292 Section II: Minimally Invasive Monitoring

Von Spiegel et al. [56] compared the clearance method of a using this test. As similar results were achieved, the authors
transpulmonary indicator dilution technique with an arterial concluded that this test could be used to measure hepatic dys-
fiberoptic thermistor catheter that assessed the ICG-circulating function associated with obstructive jaundice [68]. Reports of
curve in patients undergoing liver transplantation. They found the use of other marked compounds to assess liver function
that both methods were effective in detecting onset and main- using the breath test principles, such as 13 C-methacetin [69],
tenance of graft function in these patients. Newer technology l-[1,213C] Ornithine [70], and l-[1130 C] alanine [71] have
allows the use of assessment of ICG PDR transcutaneously. been described with promising results.
In two separate publications, Sakka et al. [57,58] suggested Other dynamic tests that are available include the antipyrine
that this technology, when compared with invasive methods, clearance test [46,47], the caffeine clearance test [47], and the
reflected ICG blood clearance with sufficient accuracy in crit- pharmacokinetics of acetaminophen. Zapater et al. [72] re-
ically ill patients to be used as a surrogate. In contrast, in a ported a higher AUC concentration and lower clearance and
model of hyperdynamic porcine endotoxemia the PDR of ICG higher elimination half-life in cirrhotics when compared with
failed to accurately substitute for direct short-term measure- healthy volunteers.
ments of ICG excretion [59]. The authors suggested that nor-
mal values of PDR of ICG should be interpreted with caution
in early, acute inflammatory conditions. As mentioned before,
ICG clearance also aids with the evaluation of the hepatic en-
Blood Flow Tests
ergy status since the excretion into bile is energy dependent. Tests to determine hepatic blood flow are also useful. Xylocaine
Chijiiwa et al. [60] correlated the biliary excretion of ICG with metabolism also evaluates hepatic blood flow [35]. The use of
the ATP levels in liver samples obtained from patients with bil- ICG has also been described for this purpose. The use of intra-
iary obstruction, and in a second study, they were able to cor- venous infusions of ICG seemed more reliable and accurate in
relate those variables with the biliary acid output [61]. They evaluation of hepatic blood flow than with the use of boluses or
concluded that biliary bile acid output and ICG excretion are intravenous injections of galactose [59]. Apparently with the
valuable parameters of hepatic energy status, which is essential use of boluses, extrahepatic accumulation of the dye occurs and
for organ viability. ICG can be considered a valuable tool to alters the results [60]. More recently, pulse dye-densitometry
assess liver function in patients after liver transplantation, at (PDD) has been used in the critically ill patient instead of blood
risk to develop, or with ongoing liver injury to assess damage tests. Mizushima et al. [61] measured effective hepatic blood
and recovery and to assess the energy status of the liver. volume (EHBV) and cardiac output (CO) using ICG-PDD [61].
They found that in septic patients, the EHBF/CO ratio was
Radiological Studies lower than that of nonseptic patients, suggesting that inade-
quate splanchnic perfusion or metabolic changes occur in septic
Another method to assess functional liver reserve is with the use
patients. In addition, the lower EHBF/CO ratio was related to
of technetium-99 diethylenetriamine penta-acetic acid galac-
a fatal outcome in septic patients. The authors concluded that
tosyl human serum albumin (99mTc-DTPA-GSA) clearance.
PDD could be a clinically useful method of assessing splanchnic
Studies using hepatic scintigraphy and more recently single-
conditions in critically ill patients. Dysfunction in one of the
proton emission computer tomography (SPECT) scan have
components of the gastrointestinal system, in this case the liver,
been described [62,63]. Hwang et al. [63] demonstrated the use
manifested by decreased metabolic [3537] capacities or hep-
of this test as a reflection of hepatic function and also suggested
atic blood flow [36,61] are related to shock states and are prob-
that predicting residual hepatic values was a good indicator of
ably an integral part of the multiorgan system failure (MOSF)
postoperative hepatic function and early prognosis after liver
cascade, highlighting the relationship of the gastrointestinal
resection. Kira et al. [62] showed that using this test before and
system with immunity.
after transjugular intrahepatic portosystemic shunt was useful
to evaluate changes in hepatic functional reserve and evalu-
ate the degree of portosystemic shunt. At this time, the test is
mostly used as a predictor of liver function after liver resection Tests of Cholestasis
and not used in the critically ill [64].
In patients with conjugated hyperbilirubinemia but without
other indicators of liver dysfunction or injury, biliary ob-
Breath Tests struction should be suspected. Alkaline phosphatase (AP), like
The use of breath tests as qualitative measurement of liver func- SGOT and SGPT, is found in a variety of different organs, but
tion has also been described. The principle behind these tests has its highest concentration in the liver. As such, it is most
is similar to the description of breaths tests used for monitor- often elevated in situations where cholestasis is present. AP
ing of gut absorption described earlier. As the carbon marked is more specific than gamma glutamyl transpeptidase (GTT)
compound is metabolized, the resulting marked carbon diox- for biliary tree inflammation, as GGT is sensitive to even mild
ide can be measured in the breath. As liver function declines, liver inflammation and/or activation of the cytochrome P-450
less of the marked CO2 will be detected in the breath. In an enzymes.
animal model of hepatectomy, Ishii et al. [65] injected l-[1- Further workup may include radiological evaluation. Hep-
(13)C] methionine and l-[1-(13)C] phenylalanine intravascu- atic iminodiacetic acid (HIDA) scan may also prove valuable in
larly and measured the exhaled 13 CO2 over 15 minutes. They differentiating the cause of cholestasis. The test reveals many
concluded that this test could qualitatively evaluate liver dys- facets of hepatic function with respect to its ability to conju-
function. In a human study, Kobayashi et al. [66] demonstrated gate bile: If the liver does not actively uptake tracer, than its
that the use of the 13 C phenylalanine test correlated well with ability to conjugate bile must be questioned. In addition, when
ICG clearance test, Child Pughs classification, and standard conjugation is not an issue, definitive anatomic localization of
liver blood tests, suggesting that this test is a useful nonin- biliary obstruction is possible. In addition, in the presence of
vasive method to determine liver functional reserve. Koeda et a functional sphincter of Oddi, it is possible to diagnose acute
al. [67] studied the validity of the 13 C phenylalanine breath cholecystitis. Further assessment of biliary architecture can be
test in both chronic cirrhosis and acute hepatitis patients and made with ultrasonography. Not only can one determine the
concluded that in both groups this test allows the noninvasive architecture of the liver and gallbladder, but one can also deter-
evaluation of hepatic function. Hepatic dysfunction associated mine the amount of intra- and extrahepatic biliary dilatation,
with obstructive jaundice in a rat model was also evaluated further delineating the source of biliary obstruction.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 30: Monitoring Gastrointestinal Tract Function 293

importance, monitoring of intestinal function is limited, pro-


CONCLUSIONS viding anatomic and physiologic information rather than an
assessment of pathophysiologic change. Assessment of absorp-
Gastrointestinal function is of vital importance in the criti- tion by sugar absorption tests and breath tests, of motility by
cally ill patient. These functions are not limited to the mere manometry, and of ischemia by tonometry and microdialysis
absorption of nutrients but are closely related with the im- are promising modalities that may help monitor the functions
mune system, particularly in the critically ill patient. Despite its of the gastrointestinal tract.

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Med 24:12681272, 1997. Aliment Pharmacol Theory 1:2936, 2004.

CHAPTER 31 RESPIRATORY MONITORING


DURING MECHANICAL VENTILATION
TODD W. SARGE, RAY RITZ AND DANIEL TALMOR

Respiratory function may be simply classified into ventilation


and oxygenation, where ventilation and oxygenation are quan- GAS EXCHANGE
tified by the ability of the respiratory system to eliminate car-
bon dioxide and form oxyhemoglobin, respectively. The goal Basic Physics of Gas Exchange
of respiratory monitoring in any setting is to allow the clini-
cian to ascertain the status of the patients ventilation and oxy- As mentioned earlier, the primary function of the respiratory
genation. The clinician must then use the data appropriately to system is gas exchange (i.e., elimination of carbon dioxide
correct the patients abnormal respiratory physiology. As with while instilling oxygen to form oxyhemoglobin). Inadequate
all data, it is imperative to remember that interpretation and ventilation and oxygenation within the intensive care setting
appropriate intervention are still the onus of the clinician, who are typically caused by hypoventilation, diffusion impairment,
must integrate these data with other pieces of information (i.e., or shunt and ventilationperfusion (VQ) mismatch.
history and physical examination) to make a final intervention. Hypoventilation is defined as inadequate alveolar ventila-
In the acutely ill patient, the principal intervention with regard tion, and it is commonly caused by drugs, neurologic impair-
to respiratory function and monitoring usually involves the ini- ment, or muscle weakness/fatigue, which results in hypercar-
tiation, modification, or withdrawal of mechanical ventilatory bia, according to the following equation:
support. This chapter focuses on respiratory monitoring for the
mechanically ventilated patient. Pa CO2 = (V CO2 /VA )k
Mechanical ventilation entails the unloading of the respira-
tory system by the application of positive pressure to achieve where Pa CO2 is the arterial partial pressure of carbon diox-
the goal of lung insufflation (i.e., inspiration) followed by ide, V CO2 the production of carbon dioxide in the tissues, V A
the release of pressure to allow deflation (i.e., expiration). the alveolar ventilation, and k the constant. Fortunately, the
These simplified goals of mechanical ventilation are achieved in institution of mechanical ventilatory support readily corrects
spite of complex and dynamic interactions of mechanical pres- hypoventilation while the underlying cause is determined and
sure with the physical properties of the respiratory system, corrected.
namely elastance (Ers ) and resistance (Rrs ). Furthermore, the Diffusion impairment is a result of inadequate time for the
patients neurologic and muscular conditions can also affect exchange of oxygen across the capillaryalveolar membrane.
the goals of respiration, and they need to be monitored and This may occur due to pathologic thickening of the membrane
evaluated as well. This chapter focuses on three specific ar- or high-output cardiac states such as sepsis. However, the rela-
eas in monitoring the mechanically ventilated patient: (a) the tive clinical significance of diffusion impairment in the intensive
evaluation of gas exchange, (b) respiratory mechanics, and (c) care unit (ICU) is debatable. This is because the hypoxemia that
respiratory neuromuscular function. results from the acute exacerbation of diffusion impairment
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Chapter 31: Respiratory Monitoring during Mechanical Ventilation 295

is usually corrected by supplemental oxygen therapy. Further- blood gas (ABG) analysis include the fact that it is a fairly exact
more, Pa CO2 is rarely affected by diffusion impairments be- representation of the current state of the patient with regard to
cause it is highly soluble and is eliminated in multiple forms, acidbase status, oxygenation, and ventilation. However, the
such as bicarbonate. limitations of blood gas analysis as a tool for monitoring gas
The most common cause of hypoxemia in the ICU is exchange are numerous, including the fact that it is invasive,
ventilationperfusion (V Q)
mismatch. One manifestation of wasteful (blood), and noncontinuous (i.e., it is only a snapshot

VQ mismatch is shunting. The true shunt fraction is the of the patients condition at the time the ABG is drawn).
amount of cardiac output that results in venous blood mixing Central and peripheral venous blood gas sampling has been
with end-arterial blood without participating in gas exchange. proposed as an acceptable surrogate to arterial blood for moni-
This has little effect on carbon dioxide tension; however, in- toring pH, Pa CO2 , and base deficit [1]. The obvious advantage
creases in shunt can lead to hypoxemia. The true shunt is ex- is mitigation of the invasiveness (i.e., patients are not required
pressed by the shunt equation as follows: to have arterial access or punctures), while the disadvantages
are the need for correlation and inability to assess oxygenation.
Qs /Qt = (Cc Ca )/(Cc Cv ) With the exception of patients undergoing cardiopulmonary
resuscitation [2], good correlation has been observed between
where Qs and Qt are the shunt and total blood flows, and Cc , arterial and venous pH and Pa CO2 in patients with acute res-
Ca , and Cv represent the oxygen contents of pulmonary end- piratory disease, with one study noting an average difference
capillary, arterial, and mixed venous blood, respectively. The of 0.03 for pH and 5.8 for Pa CO2 [1]. Another study in me-
absolute oxygen content of arterial and mixed venous blood is chanically ventilated trauma patients also demonstrated good
calculated according to the oxygen content equation: correlation between arterial and central venous pH, Pa CO2 ,
and base deficit; however, the authors concluded that the lim-
Cx = (1.34 Hb Sx O2 ) + (Px O2 0.003)
its of agreement (0.09 to 0.03 for pH and 2.2 to 10.9 for
where Cx , Sx O2 , and Px O2 are the oxygen content, saturation, Pa CO2 ) represented clinically significant ranges that could af-
and partial pressure of oxygen within arterial and mixed ve- fect management and therefore should not be used in initial
nous blood, respectively. The oxygen content of end-capillary resuscitation efforts of trauma patients [3].
blood is estimated by the alveolar gas equation as follows:
Cc = (Patm PH2 O ) Fi O2 + Pa CO2 /RQ Pulse Oximetry
where Patm and PH2 O are the partial pressures of the atmosphere Without question, pulse oximetry has been the most significant
and water (typically 760 and 47 at sea level), respectively; while advance in respiratory monitoring in the past three decades. On
Fi O2 is the concentration of inspired oxygen; Pa CO2 the arte- the basis of established oxyhemoglobin dissociation curve (Fig.
rial partial pressure of carbon dioxide; and RQ the respira- 31.1), pulse oximetry allows for the continuous, noninvasive
tory quotient. The significance of true shunt is the fact that estimate of a patients oxyhemoglobin and is expressed as a
it is not amenable to supplemental oxygen therapy. Shunted percentage of total hemoglobin. A detailed explanation of pulse
blood reenters the circulation and dilutes oxygenated blood, oximetry including the physics and limitations is provided in
resulting in a lower partial pressure of oxygen (Pa O2 ) in the Chapter 26.
arterial system. Increasing the Fi O2 will not improve oxygena-
tion since the shunted fraction of blood does not meet alveolar
gas.
VQ mismatch is the result of inequality of the normal venti- Expired Carbon Dioxide Measurements
lation/perfusion ratio within the lung. VQ mismatch is a spec-
Capnometry is the quantification of the carbon dioxide con-
trum of abnormal ratios signifying inadequate gas exchange
centration in a sample of gas. Capnography is the continuous
at the alveolar level. It is possible with supplemental oxygen
to overcome hypoxemia that is caused by an abnormal ratio
of ventilation and perfusion, which differentiates this form of
hypoxemia from true shunt. However, in the extreme, as the
VQ ratio in any alveolus approaches zero (i.e., ventilation ap-
proaches zero), it approaches true shunt as described above.
At the other end of the spectrum, as the ratio in any alveolus
approaches infinity (i.e., as perfusion approaches zero), it be-
comes physiologic dead space, which denotes alveoli that are
ventilated but not perfused. Dead space is described in greater
detail later in this chapter.

Direct Blood Gas Analysis


Monitors of gas exchange in the mechanically ventilated pa-
tient are typically directed at measurements of gas content and
their gradients from the ventilator circuit to the alveolus and
from the alveolus to the end-artery. As with most monitors,
sources of error abound at many points as gases flow down
their concentration gradients. The most accurate assessment
of gas exchange is direct measurement from an arterial blood
sample. This provides the partial pressures of carbon dioxide
(Pa CO2 ) and oxygen (Pa O2 ) in the blood as well as the pH, FIGURE 31.1. This is a schematic demonstrating a normal hemo-
base deficit, and co-oximetry of other substances such as car- globin dissociation curve with 50% saturation at Pa O2 of 27 mm Hg
boxyhemoglobin and methemoglobin. Advantages of arterial and approaching 100% saturation at a Pa O2 of 80 mm Hg.
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296 Section II: Minimally Invasive Monitoring

FIGURE 31.2. This is a schematic


representation of a capnograph wave-
form with the expiratory plateau de-
lineating the end-tidal CO2 between
30 and 40 mm Hg.

plotting of carbon dioxide over time to create a waveform (Fig. disease (COPD). Vd /Vt can also increase with dynamic hyper-
31.2). When capnography is performed on continuous samples inflation or auto-PEEP, as well as with overaggressive applica-
of gas from the airway circuit, a waveform is created whereby tion of extrinsic positive end-expiratory pressure (PEEP) due
the plateau is reported as the maximum pressure in millime- to overinflation of alveoli impeding pulmonary artery blood
ters Hg and termed end-tidal carbon dioxide, or Pet CO2 . Al- floweffectively increasing the West Zone 1 volume. Serial
though continuous capnography has limited usefulness in the measurements of Vd /Vt have been shown to correlate with out-
ICU, capnometry has many clinical uses such as early detec- come in ARDS [6] and have been used to monitor the degree of
tion of esophageal intubation. For a detailed explanation of respiratory compromise in critically ill patients [7]. However,
capnography and its uses, please refer to Chapter 26. these data have not translated into changes in treatment. Fur-
thermore, Mohr et al. [8] found no appreciable difference in
Vd /Vt while studying a series of posttracheostomy patients suc-
Dead Space Measurements cessfully weaned from mechanical ventilation compared with
those who had failed weaning.
Dead space is defined as any space in the respiratory system
that is ventilated but not perfused, such that no gas exchange
can occur. Measurement of dead space is a marker of respi- PULMONARY MECHANICS
ratory efficiency with regard to carbon dioxide elimination.
Dead space can be subdivided into several categories including
alveolar and anatomic. Anatomic dead space is the sum of the Basic Pulmonary Variables
inspiratory volume that does not reach the alveoli and, there-
fore, participate in gas exchange. For mechanically ventilated Modern ventilators allow manipulation and measurement of
patients, the anatomic dead space includes the proximal air- the airway pressures (Paw ), including peak, plateau, mean and
end-expiratory; volumes (V); and flows (V). Integration of
ways, trachea, endotracheal tube, and breathing circuit up to
the Y-adapter. In normal human subjects, anatomic dead space these measurements allows assessment of the mechanical com-
in cubic centimeters is approximately two to three times the ponents of the respiratory system. The mechanical components
ideal body weight in kilograms, or 150 to 200 cm3 . Alveolar are influenced by various disease states, and understanding
dead space is the conceptual sum of all alveoli that are venti- these relationships may allow delivery of more appropriate ven-
lated but not participating in gas exchange, otherwise described tilator support. The airway pressure (Paw ) is described by the
as West Zone 1 [4]. Physiologic dead space (Vd ) is the sum equation of motion and must be equal to all opposing forces.
of anatomic and alveolar dead space and is usually expressed For the relaxed respiratory system ventilating at normal fre-
as a ratio of the total tidal volume (Vt ) and can be calculated quencies, the major forces that oppose Paw are the elastive and
at the bedside using the modified Bohr equation: resistive properties of the respiratory system as they relate to
respectively:
the tidal volume (Vt ) and flow (V),
Vd /Vt = Pa CO2 Pexp CO2 /Pa CO2

Paw = Ers Vt + Rrs (V)
where Pa CO2 is the partial pressure of carbon dioxide and
Pexp CO2 the partial pressure of carbon dioxide in the expired where Ers and Rrs are the elastance and resistance of the respi-
tidal volume of gas. The Pexp CO2 is difficult to measure, of- ratory system, respectively.
ten requiring metabolic monitoring systems. However, volume Constant flow inflation in a relaxed, ventilator-dependent
capnography is a novel and simple approach to estimating patient produces a typical picture as depicted in Figure 31.3
Pexp CO2 , involving measurements of carbon dioxide at the Y- [9]. The rapid airway occlusion method at end inflation re-
adapter, and has been shown to correlate with more complex sults in zero flow and a drop in Paw from the peak value (peak
methods of metabolic monitoring [5]. The Pa CO2 is often es- inspiratory pressure, PIP) to a lower initial value and then a
timated as end-tidal carbon dioxide, Pet CO2 , however this is gradual decrease over the rest of the inspiratory period until a
known to be inaccurate in disease states. Therefore, determi- plateau pressure (Pplat ) is observed. The Pplat measured at the
nation of the Pa CO2 is most often measured directly by an airway represents the static end-inspiratory recoil of the entire
ABG. respiratory system [10].
Physiologic dead space, Vd /Vt , is often increased in critical Measurement of the pleural pressures would allow further
illnesses that cause respiratory failure, such as acute respiratory partitioning of these pressures into the lung (i.e., transpul-
distress syndrome (ARDS) and chronic obstructive pulmonary monary pressure, PL ) and chest wall (i.e., pleural pressure, Ppl )
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Chapter 31: Respiratory Monitoring during Mechanical Ventilation 297

Pressure Compliance and Elastance


waveform
PIP
The static compliance (Cst,rs ) of the respiratory system and its
Resistance
reciprocal, elastance (Est,rs ), are easily measured at the bed-
side using the aforementioned end-inspiratory airway occlu-
Pplat sion method to produce zero flow and thus negate the resistive
forces within the system. The elastance of the respiratory sys-
tem (Est,rs ) is simply the pressure gradient between the total
PEEP (PEEPt ) and the plateau pressure (Pplat ) divided by the
Compliance tidal volume (Vt ) to yield the following equation:
Auto-PEEP
Est,rs = (Pplat PEEPt )/Vt
PEEP
Est,rs may also be separated into its lung (EL ) and chest wall
(Ecw ) components by applying this equation to the PL and Pes
tracings obtained using Pes tracings (see Fig. 31.4) and by the
equation:

FIGURE 31.3. Schematic drawing of an airway pressure waveform Est,rs = EL + Ecw


delineating PEEP, auto-PEEP, peak inspiratory pressure (PIP), plateau The relative contributions of the lung and chest wall to the
pressure (Pplat ), resistance, and compliance. total elastance may be dependent on the etiology of respiratory
failure. By way of example, pulmonary edema, either cardio-
components using the equation: genic or as a result of ARDS, will lead to an elevated lung Est
and reduced compliance. ARDS of a nonpulmonary origin, for
Paw = PL + Ppl
example, sepsis, may also lead to edema of the chest wall and
Unfortunately, direct measurements of pleural pressure are abdominal distension. Both of these will lead to an additional
not practical in the intensive care setting. Therefore, pleural increase in the Est,rs as a result of an increase in the elastance
pressures have often been estimated by esophageal balloon of the chest wall.
catheters measuring the pressure in the esophagus (Pes ), which
lies in the proximity of the pleura at mid-lung height. This alters
the earlier equation as follows: Resistance
Paw = PL + Pes
According to Ohms law, resistance is a function of the airway
where Pes is esophageal pressure. Airway resistance
pressure gradient (Paw ) divided by flow (V).
These partitioned pressures are presented graphically in can be measured in ventilator-dependent patients by using
Figure 31.4. the technique of rapid airway occlusion during constant flow

80
40
Flow (lpm)

0
2 4 6 8 10 12 14
-40
-80
-120
50
Pairway (cm H2O)

40
Peso (cm H2O)

30
20
10
0
0 2 4 6 8 10 12 14
32
24
Pair-Peso (cm H2O)

16
8
Time (seconds)
0
2 4 6 8 10 12 14
-8
-16

FIGURE 31.4. Esophageal pressure tracing (Peso ) can be seen superimposed on the airway pressure tracing
(Pair ) during pressure control ventilation (PCV). Transpulmonary pressure has been estimated as the
difference between these pressures with specific assumptions.
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298 Section II: Minimally Invasive Monitoring

inflation. The maximum resistance (Rmax ) of the respiratory conditions, where resistance and compliance depend on vol-
system is calculated by ume, flow, and respiratory frequency.
Rmax = [Ppeak Pplat ]/V
Dynamic Measurements of the PressureVolume Curve
And the minimum resistance (Rmin ) of the respiratory system Dynamic measurement of the PV curve allows continuous
can be computed by dividing monitoring of the respiratory mechanics and in particular of the
response to ventilator changes. These measurements are done
Rmin = [Ppeak PEEPt ]/V with the patient on therapeutic ventilator settings and therefore
Rmin reflects ohmic airway resistance, while the difference may reflect more accurately the complex interaction of patient,
between Rmax and Rmin (R) reflects both the viscoelastic endotracheal tube, and ventilator. A continuous display of pres-
properties (stress relaxation) and the timeconstant variabil- sure may be obtained either proximal to the endotracheal tube
ity within the respiratory tissues (pendelluft effect). (at the patient connector or from the ventilator itself) or distal
to the endotracheal tube. This pressure may then be plotted
against tidal volume to produce a dynamic PV curve. Each of
these methods has advantages; however, the more commonly
PressureVolume Curves used proximal method suffers from the disadvantage of being
heavily influenced by the resistance of the endotracheal tube.
Static Measurements of the PressureVolume Curve Neither the peak pressure nor the end-expiratory pressures are
The gold standard of pressurevolume (PV) curve measure- accurately recorded, and this will lead to an underestimation
ment is the super-syringe method. Using a large calibrated sy- of compliance [12].
ringe, increments of volume of 50 100 mL gas are used to
inflate the lung up to a total volume of 1,000 2,000 mL. Clinical Use of the PressureVolume Curve
After each increment, the static airway pressure is measured There is a characteristic shape to the static respiratory system
during a pause lasting a few seconds during which there is no PV curve of patients with injured lungs. This shape includes
flow, and the pressure is the same in the entire system from an S-shaped inflation curve with an upper and lower inflec-
the super-syringe to the alveoli. The lung is then deflated in tion point (UIP and LIP, respectively; Fig. 31.5), an increased
the same manner and the pressure at each decrement of gas recoil pressure at all lung volumes, and reduced compliance
is recorded and the inspiratory and expiratory PV curves are (Fig. 31.6), which is seen in the slope of the inflation curve
plotted. Continued oxygen uptake from the blood during this between LIP and UIP. The LIP has often been considered the
slow inflationdeflation cycle, coupled with equalization of the critical opening pressure of collapsed lung units and has been
partial pressure of CO2 in the blood and alveoli, will lead to used as a method of setting the optimal PEEP in patients with
a decrease in the deflation volume as compared with the infla- acute lung injury (ALI). The pressure at UIP, in turn, was con-
tion volume of gas. This artifact may appear to contribute to sidered to indicate alveolar overdistension that should not be
the phenomena of hysteresis. The more important mechanical exceeded during mechanical ventilation [15]. These ideas have
cause of hysteresis is based on the slow inflation of the lung been challenged for multiple reasons. Accurate identification
during the PV curve maneuver. This slow inflation recruits or of the LIP and UIP is challenging even for experienced clini-
opens up areas of the lung with slow time constants and col- cians [16]. In addition, changes in the PV curve are not spe-
lapsed alveoli. This again will lead to a decreased expiratory cific for alveolar collapse and have been observed in saline-filled
volume and hysteresis. lungs, such as would be seen in patients with pulmonary edema
[17,18]. When applied clinically to patients mechanically ven-
Semistatic Measurements of the PressureVolume Curve tilated with ARDS, Amato et al. [19] demonstrated that use of
There are two methods for obtaining semistatic measure- the PV curve and titration of PEEP to a level that exceeds the
ments of the PV curve. These methods do not require the LIP may be part of a successful lung-protective strategy. It is
specialized skill and equipment needed for the super-syringe unclear from this study, however, what the relative importance
technique. The multiple occlusion technique uses a sequence of the higher levels of PEEP was in the context of the ventilatory
of different-sized volume-controlled inflations with an end- strategy, which included delivery of low tidal volumes and the
inspiratory pauses [11,12]. Pressure and volume are plotted use of intermittent recruitment maneuvers. Subsequent trials
for each end-inspiratory pause to form a static PV curve. If have confirmed the survival benefit in patients ventilated using
expiratory interruptions are also done, the deflation limb of the low tidal volumes but not in those ventilated with a higher level
PV curve may also be plotted. This process may take several of PEEP [20,21].
minutes to complete, but yields results close to those obtained
by static measurements. The second method is the low-flow
inflation technique. This technique uses a very small constant Separating the Lung and Chest Wall
inspiratory flow to generate a large total volume. The slope Components of Respiratory Mechanics
(compliance) of the curve is parallel with a static PV curve
only if airway resistance is constant throughout the inspira-
tion. This is likely not the case as the low flow lessens airway
Esophageal Pressure Monitoring
resistance. The low flow also causes a minimal but recognizable Ventilator-induced damage to the lungs arguably depends on
pressure decrease over the endotracheal tube, which means that the transpulmonary pressure (Paw Ppl ), whereas current rec-
the dynamic inspiratory pressurevolume curve will be shifted ommendations for management of ARDS specify limits for
to the right [13,14]. The long duration of the inspiration pro- pressure applied across the whole respiratory system and are
duces the same artifacts as the super-syringe technique, which based on pressures measured at the airway. This approach
is represented as hysteresis. Another drawback of static and could be seriously misleading if Ppl were to vary substan-
semistatic methods is that they require stopping therapeutic tially among patients. In healthy subjects and upright sponta-
ventilation while the maneuver is performed. The question has neously breathing patients, Ppl is often estimated by measuring
been raised, therefore, if these maneuvers are relevant in pre- esophageal pressure (Pes ); however, this is rarely done in pa-
dicting the mechanical behavior of the lung under dynamic tients with acute injury, possibly because of a widespread, but
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Chapter 31: Respiratory Monitoring during Mechanical Ventilation 299

Exhalation

UIP

Open lung
tidal volume
Volume

LIP

Inspiration

Pressure

FIGURE 31.5. Schematic representation of normal pressurevolume curve (PV curve) with upper and
lower inflection points (UIP and LIP, respectively) delineating the more compliant portion of the inspiratory
limb and corresponding tidal volume that has been proposed as an open lung approach to ventilation
in ARDS.

untested, belief that artifacts make Pes unreliable as an estimate accurate, but the absolute values were not [23]. Others have
of Ppl [22]. However, in a lung-injured canine model, Pelosi postulated the explicit assumption that absolute values of Pes ,
et al. [23] demonstrated good correlation at mid-lung height corrected for a positional artifact, may reliably reflect an effec-
between an esophageal balloon catheter measuring the pres- tive Ppl in critically ill patients [24].
sures in the esophagus (Pes ) and the pleural pressures measured Variations in Ppl may have contributed to inconsistent out-
by pressure-transducing wafers inserted directly in the thorax. comes among clinical trials of ventilation strategies in ARDS.
Although the absolute values of the esophageal pressures were Although one large-scale randomized trial demonstrated a sur-
not identical with the pleural pressures, Pelosi noted the excur- vival benefit from use of low tidal volume ventilation, results
sions of esophageal pressure were the same as those observed from other studies have been equivocal [20,25,26]. It is pos-
in the directly measured pleural pressures. The authors there- sible that in some patients with high Ppl , low tidal volume
fore concluded that the changes in esophageal pressures were ventilation coupled with inadequate levels of PEEP results in
cyclic alveolar collapse at end-expiration. In such cases, re-
sulting atelectrauma might negate the benefit of limiting tidal
volume. Similarly, higher levels of PEEP have been shown to
be lung protective in numerous animal models of ARDS but
have demonstrated inconsistent benefit in clinical investiga-
tions [19,21]. This too may reflect failure to account for Ppl ,
leading to under- or overapplication of PEEP in some patients
as well as misinterpretation of high-plateau airway pressures
as evidence of lung overdistension [27,28]. Measuring Pes to
estimate transpulmonary pressure may allow mechanical ven-
tilator settings to be individualized to accommodate variations
in lung and chest wall mechanical characteristics. Such an in-
dividual approach may reduce the risk of further lung injury in
ARDS [22,27,29]. This was the hypothesis of a recent single-
center, randomized control trial (EPVENT Trial) of 61 patients
by Talmor et al. in which ARDS and ALI patients with low
tidal lung-protective ventilation were randomized to a high or
low PEEP. Unique when compared with prior trials, the in-
tervention group received PEEP based on the contribution of
FIGURE 31.6. Schematic representation of altered compliance (C) the chest wall as measured by esophageal pressure manometry.
and the effect on the volumepressure (V/P) curve as occurs with pul- The control group received PEEP based on the PEEP/Fi O2 ta-
monary edema. bles from earlier trials that were created from expert opinion
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300 Section II: Minimally Invasive Monitoring

For example, complete unloading of the respiratory system is


common in the surgical operating room with general anesthe-
sia, muscle relaxants, and controlled mechanical ventilation.
However, the use of deep sedation and muscle relaxants for
prolonged periods in the ICU has deleterious effects on the lat-
ter goal of ultimately preparing critically ill patients for extuba-
tion with several studies demonstrating increases in ventilator
days, hospital length of stay, and associated costs [3537]. Fur-
thermore, assisted modes of ventilation with partial unloading
have been surmised as beneficial for maintaining the condition-
ing of the diaphragm and reducing sedation requirements in the
critical care setting [34,38]. No one has defined the ideal degree
of unloading [34], which would presumably vary by individual
and disease state. Nevertheless, it is helpful to understand and
quantify the patients neuromuscular function to facilitate un-
loading of the respiratory system, minimize patientventilator
dyssynchrony, and ultimately wean the difficult patient from
ventilatory support. This requires an understanding of respira-
tory neuromuscular physiology and how it cooperates with the
ventilator. This relationship has been termed patientventilator
interaction.

FIGURE 31.7. This graph demonstrates the correlation between pres-


sures measured in the esophagus (Pes ) and gastric pressure (Pga ). Respiratory Neuromuscular Anatomy
The respiratory system is involuntarily controlled by special-
ized neurons in the pons and medulla oblongata that control
and without individualization based on physiologic measure- both inspiration and expiration. These neurons in the brain-
ments. The primary end point was oxygenation (Pa O2 /Fi O2 ). stem coordinate many inputs and feedback loops to control res-
The authors demonstrated that ventilation with a strategy that piration and ensure adequate gas exchange. The specific types
used esophageal pressures measurements to determine PEEP of feedback can be mechanical, chemical, reflex, and behav-
settings was superior as evidenced by improved oxygenation, ioral, all of which directly affect the neurons rate and intensity
compliance, and a trend toward improved mortality [30]. of neural firing [39]. Together these neurons and their feedback
loops constitute the respiratory control center. Under normal
Gastric Pressure resting conditions, neurons in the inspiratory center stimulate
Esophageal pressure monitoring is not a trivial task, requir- contraction of the diaphragm and intercostal muscles through
ing specialized equipment and experienced operators. Gastric the phrenic and spinal nerves, which creates a negative force in
pressure may provide a reasonable surrogate measure for Ppl . the chest cavity relative to the airway (i.e., a pressure gradient),
In an earlier study, Talmor et al. [24] have demonstrated that thus allowing air to flow into the lungs (Fig. 31.8). Subsequent
there is a correlation between pressure measured in the esoph- exhalation is typically passive, and air is exhaled as a conse-
agus and gastric pressures (Fig. 31.7). This relationship may be quence of lung and chest wall elastance. However, when the res-
particularly important in patients having ARDS with extrapul- piratory center is stimulated in the presence of carbon dioxide,
monary causes, where abdominal distension may contribute acidosis, or hypoxemia, exhalation can be made more active
significantly to alveolar collapse. by contraction of abdominal and chest wall muscles. The cere-
bral cortex has the ability to take control of the respiratory
Bladder Pressure system by overriding the brainstem to change the frequency,
depth, and rhythm of respirations. This is of minimal concern
An alternative measurement of intra-abdominal pressure may in the mechanically ventilated patient, whose cerebral cortex is
be obtained by measuring pressure in the urinary bladder [31]. sedated, by either medications or illness, such that respiratory
Instilling 50 to 100 mL of sterile water through the Foley neuromuscular function is typically under the control of the
catheter, clamping the catheter, and measuring the resulting brainstem as described earlier.
bladder pressure has been shown to correlate well with intra- The muscular component of the respiratory system has been
abdominal pressure measured through a gastric tube [32]. described as a pump that when stimulated creates a pressure,
These pressures have also been shown to correlate well with Pmus [39]. During assisted mechanical ventilation, this pressure
esophageal pressures [33]. Studies are still required to validate can be added to a second pump, which is the airway pressure
use of any of these measurements in the clinical care of patients generated by the ventilator, Paw . The sum of these two pres-
with respiratory failure. sures, PT , provides the total driving pressure for inspiratory
flow [39]. Although neglecting inertia, the equation for mo-
tion in the respiratory system states that PT is dissipated while
Respiratory Neuromuscular Function overcoming the elastive and resistive properties of the lungs as
follows:
During mechanical ventilation, the goal of the clinician is to un-
PT = Pmus + Paw = (Ers Vt ) + (Rrs V) (1)
load the patients failing respiratory system and thereby reduce
the work of breathing in the setting of respiratory failure [34]. where the variables represent elastance (Ers ), tidal volume (Vt ),
Obviously, this goal is temporary with the later goal of wean- in the respiratory system [39].
resistance (Rrs ), and flow (V)
ing mechanical ventilation once the patient begins to recover Since the ventilator-generated pressure, Paw , is intended to un-
from his or her disease process. To accomplish these goals, the load the patients respiratory muscles, it should be synchronous
clinician needs to have an understanding of the patients respi- with the neural impulses generated by the respiratory center
ratory function, which impacts each of these goals differently. and thus Pmus . To be synchronous with the patients neural
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Chapter 31: Respiratory Monitoring during Mechanical Ventilation 301

60

40
Flow (lpm)

20

0
2 4 6 8 10 12 14
-20

-40

24
Pairway (cm H2O)

A
Peso (cm H2O)

16

8
B
0
0 2 4 6 8 10 12 14
600
500
Volume (mL)

400
300
200
100
Time (seconds)
0
0 2 4 6 8 10 12 14

FIGURE 31.8. Spontaneous ventilation with continuous positive airway pressure (CPAP) at 7.5 mm Hg.
Airway and esophageal pressure tracings are superimposed and marked as A and B, respectively. Note
the onset of inspiration and flow, marked by the first vertical line, as esophageal (Peso ) and airway (Pair )
pressures separate, creating a pressure gradient. Flow then ceases, as marked by the second vertical line,
when the expiratory valve is opened on the ventilator and airway pressure quickly decreases.

inspiration, the ventilator would need to initiate support si- an esophageal pressure monitor and correlates with oxygen re-
multaneously with the patients neural firing at the onset of quirements of breathing, is considered superior for quantifying
inspiration, continue this support throughout the neural firing, a patients effort and degree of unloading [34]. This is a calcula-
and stop support at the end of neural firing. In reality, this tion of the difference in the time integrals between esophageal
goal is virtually impossible, as currently there is no practical pressure, Pes , during assisted breathing and the recoil pressure
monitor for efferent motor neurons of the respiratory system. of the chest wall during passive breathing at a similar tidal
Rather than monitoring neural impulses, modern ventilators volume and flow [40].
sense changes in pressure and flow within the circuit in an ef-
fort to match the patients respiratory cycle. The variables that
we discuss regarding the patientventilator interaction include Airway Occlusion Pressure
ventilator triggering, cycling-off, and delivery of gas between
these two events (i.e., the posttrigger phase). However, it is es- Airway occlusion pressure at 0.1 seconds (P0.1 ) is an indicator
sential to first define some of the measures of respiratory drive of respiratory drive and is determined by measuring the pres-
and effort that are commonly used to assess patientventilator sure in the airway a tenth of a second after the onset of inspira-
interaction and weaning such as work of breathing, pressure tion beginning at functional residual capacity (FRC). This has
time product (PTP), airway occlusion pressure, maximal inspi- been shown to correlate well with work of breathing during
ratory force, vital capacity (VC), and rapid shallow breathing pressure support ventilation [40]. Therefore, several authors
index (RSBI). have advocated its use as a potential predictor for discontinua-
tion of mechanical ventilation [4144]. The threshold value for
P0.1 of 6 cm H2 O appeared to delineate success versus failure
Work of Breathing in one such study, although this value was variable among au-
thors. Although the utility of this measurement is still debated,
Patient respiratory effort is typically discussed and quantified it has been incorporated into several commercially available
via some measure of the patients work of breathing. Work is ventilators.
defined as the force acting on an object to cause displacement of
that object. Therefore, mechanical work of breathing includes
the measurement of a force required to create a change in vol- Maximal Inspiratory Force
ume of gas and is expressed in Joules per liter. However, mea-
surements that are based on volume frequently fail to account Maximal inspiratory pressure (MIP), also known as negative
for the work done by the diaphragm and respiratory muscles inspiratory force, is another marker of respiratory muscle func-
during isometric contraction against a closed valve [40], as oc- tion and strength and is determined by measuring the maxi-
curs before triggering in some assisted modes of ventilation. mum pressure that can be generated by the inspiratory muscles
The PTP, which measures swings in intrathoracic pressure by against an occluded airway beginning FRC. A normal value is
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302 Section II: Minimally Invasive Monitoring

considered to be approximately 80 cm H2 O, with respiratory As a criterion for extubation, the RSBI has had mixed suc-
compromise typically observed at values less than 40% of nor- cess. Values of 100 to 105 breaths per minute per liter are
mal. The major disadvantage and limitation of this measure- typically used as a cutoff to predict extubation success from
ment is the fact that it is extremely effort dependent, which failure. The RSBI is limited by the fact that rapid and shal-
can make interpretation difficult in severely ill, sedated, and low breathing, although sensitive indicators of respiratory dis-
neurologically impaired patients. tress, are not specific. For example, pain and anxiety are also
consistent with an abnormally high RSBI and are common-
place among critically ill patients weaning from mechanical
Vital Capacity ventilation.

Vital capacity is the sum of tidal volume, inspiratory reserve


volume, and expiratory reserve volume. Forced vital capacity PATIENT VENTILATOR
(FVC) is measured by instructing a patient to inspire maxi-
mally to total lung capacity (TLC), followed by forced expira- INTERACTION
tion while measuring the expired volume as the integral of the
flow rate. FVC has also been used as an indicator of respiratory VentilatorTriggering Variable
muscle function. However, similar to MIP, FVC is also effort de-
pendent and therefore can lead to variable results. With limited During assisted modes of ventilation, the patients inspiratory
success, it has been used to monitor trends in respiratory mus- effort is sensed by the ventilator, which is then triggered
cle strength in patients with neurologic impairment and muscle to deliver support at a preset volume or pressure (Fig. 31.9).
disorders such as cervical spine injury, myasthenia gravis, and There are two distinct methods of triggering the ventilator
Guillain-Barre [4547]. pressure and flow. Pressure triggering depends on patient in-
spiratory effort, creating a change in pressure that exceeds a
preset requirement (typically2 cm H2 O) to open the inspi-
Frequency/Tidal Volume Ratio ratory valve on the ventilator and initiate ventilator support.
Likewise, flow triggering depends on patient inspiratory effort,
Respiratory distress is typically marked by tachypnea and de- creating flow detected by a flow meter within the inspiratory
creased tidal volumes, leading to inadequate ventilation and limb that exceeds a preset threshold (typically 2 L per minute)
increases in Pa CO2 secondary to disproportionate ventilation for triggering the ventilator support. The significant difference
of anatomic dead space and inadequate alveolar ventilation. between these two triggering criteria is the presence of a closed
Therefore, the ratio of frequency to tidal volume, also known demand valve in the inspiratory limb in pressure-triggered ven-
as the RSBI, has been used to gauge respiratory distress and tilators. In general, flow triggering has been considered superior
facilitate weaning and readiness for extubation [43,4850]. to pressure-triggered algorithms in that it is believed that the

60

40
Flow (lpm)

20

0
10 20 30
-20

-40

24
A
Pressure (cm H2O)

16

0
0 10 20 30
600
500
Volume (mL)

400
300
200
100
Time (seconds)
0
0 10 20 30

FIGURE 31.9. Normal triggering in assisted-control ventilation. The circles marked A denote the pressure
and flow that correspond to patient neural inspiration that is detected by the ventilator and leads to delivery
of a mechanical breath.
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Chapter 31: Respiratory Monitoring during Mechanical Ventilation 303

work of breathing is less in a system that does not require an fective triggering can create a challenge to the clinician when
initial inspiratory effort against this closed valve. Many stud- attempting to optimize the ventilator settings. In general, it is
ies have compared flow triggering and pressure triggering with helpful to reduce the trigger threshold to a point where the de-
respect to work of breathing with most showing significant lay between neural firing and ventilator support is minimized
advantages in favor of flow-triggered systems [5153]. This is without allowing autotriggering to occur.
partially explained by the fact that flow-triggering results in
improved responsiveness with shorter delay between onset of
diaphragm contraction and ventilator triggering [53]. Cycle-Off Variable
The main variable that can be controlled on the ventilator
with regard to triggering is termed sensitivity. Typical values Neurons in the respiratory center continue firing beyond ven-
for pressure triggering are 1 to 2 cm H2 O, while those for flow tilator triggering and throughout inspiration. The cessation of
triggering are 2 to 3 L per minute. The sensitivity threshold firing is an important time point in the respiratory cycle and
is important because it is required to strike a balance between marks the beginning of expiration. The neural inspiratory time
two main problems associated with triggering. First, if the sen- is often variable from breath to breath [34]. This can lead
sitivity is set too low, patients may experience autotriggering, in to considerable dyssynchrony in controlled modes of ventila-
which pressure and flow changes that occur from sources of ar- tion such as assisted-control, pressure-control, and intermittent
tifact such as cardiac oscillations, water in the circuit, patient mandatory ventilation, where cycling-off of the ventilator
movement, or resonance within the system lead to irregular into expiration is a function of the inspiratory time (Ti ) and is
breathing patterns and dyssynchrony. Second, sensitivity set- generally constant from one breath to the next. This can lead
tings that are too high will lead to ineffective triggering, which to increased sedation requirements that are inconsistent with
has the consequences of increased and wasted work and energy the goal of ventilator weaning, as mentioned earlier. Ideally, the
(Fig. 31.10). Ineffective triggering is also common in the setting ventilator should be able to detect the end of neural firing and
of dynamic hyperinflation, as seen in obstructive disorders such react accordingly to halt the inspiratory pressure supplied. This
as asthma and COPD. In the setting of obstructive diseases, dy- is one of the goals and advantages of the supportive modes
namic hyperinflation leads to elevations in the intrinsic PEEP of ventilation such as pressure support ventilation. That is,
(PEEPi ) above a critical threshold such that the patients res- supportive modes of ventilation have the ability to detect pa-
piratory drive is insufficient to overcome the elastic recoil of tient expiration and stop ventilator inspiration such that the
the lung and chest wall and trigger the ventilator [34]. Clearly, Ti is variable. This can be accomplished by measuring flow or
this is also disadvantageous to the patient in terms of work pressure changes within the circuit. As neural firing ceases and
of breathing and may contribute to ventilator dyssynchrony. Pmus decreases to baseline with muscle relaxation, total pres-
Leung et al. [54] demonstrated that ineffective trigger attempts sure and thus flow should decrease according to the elastive
required 38% increases in patient effort as compared to suc- and resistive properties of the lung according to the equation
cessfully triggered breaths. Obviously, autotriggering and inef- of motion previously described. Typically, support modes have

80
A B
Flow (lpm)

40

0
10 20 30

-40

50

40
Pairway (cm H2O)
Peso (cm H2O)

30

20

10

0
10 20 30
-10
500

400
Volume (mL)

300

200

100
Time (seconds)
0
0 10 20 30

FIGURE 31.10. This pressure and flow tracing demonstrated failed trigger attempts that can be appreci-
ated by the negative deflections in the expiratory limbs in the flow waveform and delineated by lines A
and B.
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304 Section II: Minimally Invasive Monitoring

60
40
A
20
Flow (lpm))

0
10 20 30
-20
-40
-60
32
Pressure (cm H2O)

24

16

0
10 20 30
1000
800
Volume (mL)

600
400
200
Time (seconds)
0
0 10 20 30

FIGURE 31.11. The pressure and flow waveforms demonstrate active recruitment of expiratory muscles
to terminate ventilator inspiration. Note the time point marked by line A in which flow decreases rapidly
corresponding to a sharp increase in the airway pressure due to active exhalation.

60
40
20
Flow (lpm)

0
10 20 30
-20
-40
-60
60
50 A
Pairway (cm H2O)

40
Peso (cm H2O)

30
20
10
0
-10 10 20 30
800

600
Volume (mL)

400

200
Time (seconds)
0
0 10 20 30

FIGURE 31.12. The pressure and flow waveforms above demonstrate the classic depressions on the
inspiratory airway (Pair ) pressure tracing in a patient with an elevated respiratory drive as highlighted by
circle A. Peso , esophageal pressure.
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Chapter 31: Respiratory Monitoring during Mechanical Ventilation 305

software that detects a preset decrement in flow, which in turn modes of mechanical ventilation in an effort to decrease the
leads to cycling off the inspiratory support. This preset thresh- work of breathing and intrinsic PEEP in these situations. How-
old can be an absolute value of flow or a percentage of maxi- ever, a recent series of studies has shown that this may in fact
mum flow in the circuit, or both. Often, an increase in pressure be counterproductive due to a phenomenon now recognized
that exceeds the programmed support level will also signal the as flow-associated tachypnea [34]. Puddy and Younes [56]
ventilator to stop inspiration and open the expiratory valve as demonstrated this phenomenon by adjusting inspiratory flow
well. in awake volunteers breathing on a volume-cycled ventilator
Just as with triggering, the cycle-off variable can be a source in assisted-control mode in which inspiratory Ti was variable.
of serious tribulations with the patientventilator interaction. Laghi et al. [57] later delineated the contributions of flow, tidal
For example, in the setting of decreased lung elastance, such as volume, and inspiratory time in their study in which flow was
emphysematous lung disease, flow may not diminish enough increased from 60 to 90 L per minute and balanced with tidal
to be detected properly despite a drop in Pmus at the end of volume settings of 1.0 and 1.5 L to maintain a constant inspira-
neural inspiratory time. This can lead to patient discomfort tory time, where frequency did not change. Furthermore, they
and was studied by Jubran et al. [55], who noticed that 5 out were able to show that imposed ventilator inspiratory time dur-
of 12 patients with COPD required active exhalation to cy- ing mechanical ventilation can determine frequency indepen-
cle off the ventilator during pressure support ventilation at dently of delivered inspiratory flow and tidal volume. There-
20 cm H2 O. Active exhalation is counterproductive to both fore, the clinician must consider the counteracting variables
the primary goal of respiratory muscle unloading and venti- of flow, tidal volume, and inspiratory time when attempting
lator synchrony (Fig. 31.11). Furthermore, active exhalation to ventilate patients with elevated respiratory drive in acute
will increase transpulmonary pressure, which can lead to pre- respiratory failure and how one may negatively influence the
mature airway closure and increased intrinsic PEEPi as closing other.
capacity increases.

SUMMARY
Inspiratory Flow Variable
Respiratory monitoring is a complicated task in the critically
Inspiratory flow is now being recognized as an important pa- ill patient who requires mechanical ventilation. The clinician
rameter in assisted modes of ventilation. Critically ill patients in must carefully balance a plethora of data acquired from study-
acute respiratory failure often have elevated respiratory drives ing variables of gas exchange, pulmonary mechanics, neuro-
that appear to demand greater flow to overcome the resistance muscular function, and patient ventilator interactions. Skilled
of the failing respiratory system and ventilator breathing cir- intensive-caretrained personnel must then process these data
cuit [34]. Classically, this appears as a depression on the in- so that a plan of respiratory support, often with mechanical
spiratory limb of the airway pressure tracing and has been de- ventilation, can be instituted. This plan must proceed in such a
scribed by some practitioners as flow hunger (Fig. 31.12). way that the patient is safely ventilated and oxygenated with-
Clinically, the response has been to increase flow, which typi- out imposing the undue harm that is associated with injurious
cally ranges between 30 and 80 L per minute during assisted and careless methods of ventilation.

References
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40. Jubran A: Advances in respiratory monitoring during mechanical ventilation. 56. Puddy A, Younes M: Effect of inspiratory flow rate on respiratory output in
Chest 116(5):14161425, 1999. normal subjects. Am Rev Respir Dis 146(3):787789, 1992.
41. Capdevila X, Perrigault PF, Ramonatxo M, et al: Changes in breathing pat- 57. Laghi F, Karamchandani K, Tobin MJ: Influence of ventilator settings in de-
tern and respiratory muscle performance parameters during difficult wean- termining respiratory frequency during mechanical ventilation. Am J Respir
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SECTION III CARDIOVASCULAR PROBLEMS AND


CORONARY CARE
AKSHAY S. DESAI PATRICK T. OGARA

CHAPTER 32 APPROACH TO THE PATIENT


WITH HYPOTENSION AND HEMODYNAMIC
INSTABILITY
MICHAEL M. GIVERTZ AND JAMES C. FANG

Hypotension and hemodynamic instability are frequently en- rial line should be considered, especially if vasoactive medica-
countered clinical problems in the intensive care setting. When tions are employed. Central venous catheterization should also
the mean arterial blood pressure falls below approximately be considered to monitor intravascular volume, since volume
60 mm Hg, end-organ perfusion becomes compromised and status is often dynamic in the hypotensive patient and multi-
is manifested clinically as cool skin, decreased urine output, ple mechanisms of hypotension may be simultaneously present.
and altered mental status. Cornerstones of management in- Foley catheterization should also be employed to assess hourly
clude volume resuscitation and therapy directed toward the urine output as a surrogate for end-organ perfusion.
underlying cause of hypotension (e.g., cardiac pacing for brady- The history and physical examination should be directed
cardia, cardioversion or defibrillation for tachyarrhythmias, toward establishing the primary mechanism and etiology of
blood transfusion for gastrointestinal bleeding, corticosteroids hypotension. Primary mechanisms include hypovolemia, low
for adrenal insufficiency). When these measures fail to restore cardiac output, and vasodilation. Assessing volume status is
blood pressure and vital organ perfusion or while awaiting their critical; if not discernible from the bedside evaluation (jugular
availability, administration of intravenous vasoactive agents venous pressure, skin turgor, urine output, orthostasis), inva-
may be necessary. This chapter reviews the general manage- sive measurement of the central venous pressure should be ob-
ment of the hypotensive patient with an emphasis on coronary tained with placement of a central venous catheter. If there are
care and the pharmacologic properties of commonly used va- clinical reasons to suggest a dissociation of right and left ven-
sopressor and positive inotropic agents. An overview of shock tricular hemodynamics (i.e., right ventricular infarction), pul-
(see Chapter 157), volume resuscitation (see Chapter 158), sep- monary artery catheterization may be required to measure the
sis (see Chapter 159), the use of intra-aortic balloon coun- left ventricular filling pressure. Warm well-perfused skin and
terpulsation and mechanical circulatory support devices (see extremities despite hypotension may suggest low systemic vas-
Chapter 45) are discussed elsewhere. cular resistance and a vasodilatory state, whereas cool clammy
skin and extremities suggest vasoconstriction as a compen-
satory response to a low output syndrome. A narrow pulse
pressure may also suggest reduced cardiac output. If a putative
GENERAL APPROACH TO THE mechanism of hypotension cannot be ascertained from bed-
HYPOTENSIVE PATIENT IN THE side assessment, pulmonary artery catheterization can be used
to characterize the hemodynamic profile. This strategy is es-
CORONARY CARE UNIT pecially useful when more than one mechanism is present (for
example, a large myocardial infarction complicated by pneu-
The assessment of the hypotensive patient begins with accu- monia, leading to cardiogenic and vasodilatory shock).
rate measurement of the blood pressure and rapid correlation Initial management strategies are directed at the primary
with clinical signs of hypoperfusion. Blood pressure should be etiology of hypotension and addressed later in this chapter.
measured in both arms and confirmed by another examiner. In general, therapy is guided by the primary pathophysiologic
This practice is especially important when automated devices mechanism underlying the hypotension (e.g., volume resusci-
are used to make these measurements in the setting of tachy- tation for hypovolemia, positive inotropes for low cardiac out-
arrhythmias or respiratory distress. In patients with peripheral put, vasopressors for vasoplegia). The pace and aggressiveness
arterial disease, upper extremity blood pressure should also be of therapeutic intervention are guided by the presence or ab-
compared to measurements in the legs in the supine position. In sence of clinical signs of hypoperfusion. For example, holding
rare circumstances, true central aortic pressure may differ sig- vasodilators may be sufficient in the hypotensive patient with-
nificantly from peripherally obtained blood pressures and can out changes in mental status or urine output. In contrast, the
only be confirmed by invasive measurement during diagnostic acutely hypotensive patient with clinical shock needs rapid re-
catheterization. This situation should be suspected when clin- suscitation with intravascular volume expansion and usually
ical features of hypoperfusion do not accompany low blood vasoactive therapy.
pressure.
Hypotension is generally defined as a mean arterial pressure
of less than 60 mm Hg and/or a systolic blood pressure less than
100 mm Hg. However, higher values may be consistent with ADRENERGIC RECEPTOR
clinically relevant hypotension if there are concomitant clini- PHYSIOLOGY
cal signs of hypoperfusion such as mental confusion, oliguria,
pallor, and cool extremities. If clinically relevant hypotension Most vasopressor and positive inotropic agents currently avail-
cannot be rapidly corrected, invasive monitoring with an arte- able for use are sympathomimetic amines that exert their action

307
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308 Section III: Cardiovascular Problems and Coronary Care

by binding to and stimulating adrenergic receptors. To better


understand the similarities and differences among these agents, COMMONLY USED
a basic knowledge of adrenergic receptor distribution and func- VASOPRESSORS AND POSITIVE
tion is required [1].
The adrenergic receptors that are most relevant to the man-
INOTROPES
agement of hypotension are the 1 , 1 , and 2 receptors. 1 - The armamentarium of vasoactive agents has changed little
Adrenergic receptors are present in smooth muscle cells of since the 1980s. Commonly used drugs with vasopressor activ-
many vascular beds, including the arterioles supplying the skin, ity are dopamine, epinephrine, norepinephrine, phenylephrine,
mucosa, skeletal muscle, and kidneys, as well as the peripheral and ephedrine. Vasopressin is a newer alternative to adrenergic
veins. 1 -Adrenergic stimulation causes vasoconstriction and vasopressors. Agents with positive inotropic activity that are
is the most common mechanism of vasopressor action. The useful for the treatment of hypotension include dobutamine,
presence of 1 receptors has also been demonstrated in the my- dopamine, epinephrine, and isoproterenol. Table 32.1 summa-
ocardium, where stimulation appears to result in a positive in- rizes the receptor activity and hemodynamic effects of these
otropic effect with little change in heart rate. 1 -Adrenergic drugs.
receptors are the predominant adrenergic receptor type in
the heart and they mediate positive inotropic, chronotropic
and lusitropic responses. Stimulation of 2 -adrenergic recep- Dopamine
tors causes relaxation of smooth muscle cells in bronchial,
gastrointestinal, and uterine muscle, as well as vasodilation Dopamine is an endogenous catecholamine that functions as
in skeletal muscle. 3 -adrenergic receptors, which are located a central neurotransmitter and a synthetic precursor of nore-
mainly in adipose tissue, are involved in the regulation of lipol- pinephrine and epinephrine. When administered intravenously,
ysis and thermogenesis and do not play a role in hemody- the effects of dopamine are mediated by dose-dependent stimu-
namic stability. Other relevant receptors are the dopaminer- lation of dopaminergic and adrenergic receptors, and by stim-
gic receptors (DA1 and DA2 ), which mediate renal, coronary, ulation of norepinephrine release from nerve terminals.
cerebral, and mesenteric vasodilation, and cause a natriuretic At low doses (less than 5 g per kg per minute), dopamine
response. predominantly stimulates dopaminergic receptors in renal,
The receptor selectivity of sympathomimetic amines can be mesenteric, and coronary vessels with minimal adrenergic ef-
drug and dose dependent. For example, 2 receptors are more fects. In normal subjects, so-called renal-dose dopamine aug-
sensitive to epinephrine than are 1 receptors. Thus, at low ments renal blood flow, glomerular filtration rate, and natriure-
doses of epinephrine, the vasodilatory effect of 2 receptors sis, with little effect on blood pressure. Low-dose dopamine
predominates, whereas at high doses, 1 -mediated vasocon- has frequently been used by itself or in combination with
striction overcomes the 2 effect and increases systemic vascu- other drugs as a renoprotective agent. However, the effi-
lar resistance. The dose-dependent actions of dopamine have cacy and safety of this strategy remain controversial [2]. Al-
also been well established. though a recent study demonstrated renal vasodilatory effects
The overall clinical effects of vasoactive agents depend not of dopamine in patients with heart failure [3], a randomized
only on the outcome of direct adrenergic receptor stimula- placebo-controlled trial in 328 critically ill patients with evi-
tion, but also on the reflex response of homeostatic forces. dence of early renal dysfunction demonstrated no protective
For example, stimulation of 1 -adrenergic receptors by nore- effect of low-dose dopamine on renal function and no differ-
pinephrine would be expected to cause an increase in heart ence in ICU or hospital length of stay [4]. Moderate doses
rate; however, norepinephrine-mediated 1 -adrenergic stim- of dopamine (5 to 10 g per kg per minute) stimulate 1 -
ulation induces a reflex increase in vagal tone that cancels adrenergic receptors in the myocardium, augmenting cardiac
out its positive chronotropic effects. The action of some output by increasing contractility and, to a lesser extent, heart
drugs (e.g., dopamine and ephedrine) is further complicated rate (Fig. 32.1). In addition, venoconstriction mediated by sero-
by their ability to stimulate release of stored endogenous tonin and dopaminergic receptors may occur [5]. At higher
catecholamines. doses (greater than 10 g per kg per minute), 1 -adrenergic

TA B L E 3 2 . 1
DOSE RANGE, RECEPTOR ACTIVITY, AND PREDOMINANT HEMODYNAMIC EFFECTS OF VASOACTIVE DRUGS
COMMONLY USED TO TREAT HYPOTENSION

Systemic
Heart Cardiac vascular
Drug Dose range Dopaminergic 1 1 2 rate output resistance

Dobutamine 2.520 g/kg/min + +++ ++


Dopamine 15 g/kg/min +++
510 g/kg/min ++ + ++
1020 g/kg/min ++ +++ ++
Epinephrine 110 g/min +++ ++ ++
Isoproterenol 210 g/min +++ +++
Norepinephrine 0.530 g/min +++ ++
Phenylephrine 40180 g/min +++
Ephedrine 1025 mg IV q510 min ++ ++ ++
Vasopressin 0.010.05 U min
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Chapter 32: Approach to the Patient with Hypotension and Hemodynamic Instability 309

90 receptor stimulation predominates, resulting in systemic ar-


teriolar vasoconstriction. The overall effects of dopamine at
Heart rate (beats/min)

8.0 the highest doses resemble those of norepinephrine (see later).


However, it should be remembered that there is a great deal of
overlap in the dose-dependent effects of dopamine in critically
80 ill patients [1,2].
6.0 Moderate- to high-dose dopamine is a mainstay in the treat-
0 2.0 4.0 ment of hypotension. In studies of fluid-resuscitated patients
10.0 with septic shock, dopamine produced a mean increase in mean
0 2.5 5.0 7.5 arterial pressure of approximately 25%, primarily owing to an
70
increase in cardiac index and, to a lesser extent, systemic vas-
cular resistance [2]. In the setting of hyperdynamic septic shock
30 when excessive vasodilation is the primary source of hypoten-
sion, addition or substitution of a more potent -adrenergic ag-
8.0 onist such as norepinephrine may be more effective. Moreover,
Pulmonary capillary wedge pressure (mm Hg)

28
evidence of worsening splanchnic oxygen utilization with the
use of high-dose dopamine has made it a less attractive agent.
26 By itself or in combination with other agents, dopamine may
6.0 be used at moderate doses in the management of patients with
4.0 acute decompensated heart failure and hypotension. Venodilat-
24
ing agents (e.g., nitroprusside and nitroglycerin) may be added
to moderate the tendency of dopamine to increase cardiac-
22
filling pressures [6]. Dopamine may also be combined with
dobutamine for added inotropic effects or used at low doses
20 to augment diuresis [7], although the benefits of renal-dose
0
2.0 dopamine remain controversial and other agents may be more
0 effective for preserving renal function in critically ill patients
18 2.5
[8].
The use of dopamine is associated with several adverse ef-
16 5.0
fects, including tachycardia, tachyarrhythmias, and excessive
7.5 10.0 vasoconstriction. Although these effects are generally dose de-
14 pendent, in individual patients there may be substantial overlap
of receptor affinity such that even at low doses dopamine may
result in toxicity. In patients with ischemic heart disease, in-
1,600 0 creased myocardial oxygen consumption coupled with some
degree of coronary vasoconstriction with high-dose dopamine
Total systemic resistance (dynes/cm/sec5)

8.0
can result in myocardial ischemia. As with other positive in-
otropes, dopamine can increase flow to poorly oxygenated re-
gions of the lung and cause shunting and hypoxemia. In addi-
1,400 2.0 tion, dopamine has been shown to depress minute ventilation
4.0
2.5 6.0 in normoxic heart failure patients [9]. When dopamine is used
in patients with acute decompensated heart failure, increased
5.0 venous tone and pulmonary arterial pressure may exacerbate
1,200 pulmonary edema in the setting of already high cardiac filling
7.5 pressures. Despite these caveats, oxygen saturation generally
10.0 remains constant due to improved hemodynamics.
There is mounting evidence that dopamine adversely effects
splanchnic perfusion at doses usually required to treat septic
1,000 shock. A small, randomized study of patients with sepsis us-
ing selective splanchnic and hepatic cannulation showed that
infusion of dopamine was associated with a disproportionate
increase in splanchnic oxygen delivery compared with oxygen
2.50 3.00 3.50 extraction (65% vs. 16%). In contrast, norepinephrine pro-
Cardiac index (L/min/m2) duced better-matched increases in oxygen delivery and extrac-
tion (33% vs. 28%) [10]. Another study showed that in patients
FIGURE 32.1. Comparative effects of dopamine (closed circles) and with septic shock randomly assigned to treatment with nore-
dobutamine (open triangles) on heart rate, pulmonary capillary wedge
pressure, and total systemic resistance in patients with advanced heart
pinephrine or dopamine, gastric intramucosal pH worsened
failure. The numbers shown on the figures are infusion rates in g significantly in patients treated with dopamine despite similar
per kg per minute. These data demonstrate that dopamine at doses improvements in mean arterial pressure [11]. Thus, the use of
greater than 2 to 4 g/kg/min exerts a vasoconstrictor effect and in- dopamine in septic shock may be associated with splanchnic
creases heart rate and left ventricular filling pressure. [Adapted from shunting, impairment of gastric mucosal oxygenation, and in-
Leier CV, Heban PT, Huss P, et al: Comparative systemic and regional creased risk of gastrointestinal bleeding [2].
hemodynamic effects of dopamine and dobutamine in patients with
cardiomyopathic heart failure. Circulation 58:466475, 1978, with
permission.]
Epinephrine
Epinephrine is an endogenous catecholamine that is a po-
tent nonselective agonist of - and -adrenergic receptors.
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310 Section III: Cardiovascular Problems and Coronary Care

Norepinephrine Epinephrine Isoproterenol


PULSE 100
RATE
(min) 50
180
BLOOD
PRESSURE 120
(mm Hg)
60
10 g/min 10 g/min 10 g/min

FIGURE 32.2. Cardiovascular effects of


PERIPHERAL intravenous infusions of norepinephrine,
RESISTANCE epinephrine, and isoproterenol in normal
human subjects. [Modified from Westfall
TC, Westfall DP: Adrenergic agonists and
antagonists, in Brunton LL (ed): Good-
0 15 0 15 0 15 man & Gilmans The Pharmacological
Basis of Therapeutics. 11th ed. New York,
TIME McGraw-Hill, 2005, pp 237295, with
(min) permission.]

Stimulation of myocardial 1 and 2 receptors increases con- The main cardiovascular effect of norepinephrine is dose-
tractility and heart rate, resulting in a rise in cardiac output (Fig. dependent arterial and venous vasoconstriction owing to -
32.2). Cardiac output is further augmented by an increase in ve- adrenergic stimulation (Fig. 32.2). The positive inotropic and
nous return as a result of 1 -mediated venoconstriction. Blood chronotropic effects of 1 stimulation are generally counterbal-
flow to skeletal muscles is increased owing to 2 -mediated va- anced by the increased afterload and reflex vagal activity in-
sodilation. With very low-dose infusions of epinephrine (0.01 duced by the elevated systemic vascular resistance. Thus, heart
to 0.05 g per kg per minute), -adrenergicmediated posi- rate and cardiac output usually do not change significantly,
tive chronotropic and inotropic effects predominate. Diastolic although cardiac output may increase or decrease depending
blood pressure and overall peripheral vascular resistance may on vascular resistance, left ventricular function, and reflex re-
actually decrease owing to vasodilation in skeletal muscle. With sponses [5].
higher doses of epinephrine, stimulation of -adrenergic recep- Norepinephrine, when infused at doses ranging from 0.5
tors in precapillary resistance vessels of the skin, mucosa, and to 30.0 g per minute, is a potent vasopressor. Although gen-
kidneys outweighs 2 -mediated vasodilation in skeletal muscle, erally reserved as a second-line agent or used in addition to
causing increased mean and systolic blood pressure [1]. other vasopressors in cases of severe distributive shock, nore-
Epinephrine plays a central role in cardiovascular resuscita- pinephrine is emerging as an agent of choice for the manage-
tion (see Chapter 23) and the management of anaphylaxis (see ment of hypotension in hyperdynamic septic shock [14,16]. In
Chapter 194). Epinephrine is also used to reverse hypotension a small, prospective double-blind trial, Martin et al. [17] ran-
with or without bradycardia after cardiopulmonary bypass or domized patients with hyperdynamic septic shock to dopamine
cardiac transplantation [12]. Because of its adverse effects on or norepinephrine titrated to a mean arterial pressure greater
splanchnic and renal blood flow and potential for inducing than or equal to 80 mm Hg or systemic vascular resistance
myocardial ischemia and tachyarrhythmias, epinephrine has greater than 1,100 dynes per second per cm5 , or both. Al-
generally been regarded as a second-line agent in the man- though only 5 of 16 patients randomized to dopamine were
agement of septic shock [2,13]. However, a recent random- able to achieve these endpoints, 15 of 16 patients randomized
ized trial showed no difference in efficacy or safety between to norepinephrine were successfully treated with a mean dose
epinephrine alone versus norepinephrine plus dobutamine in of 1.5 g per kg per minute. Moreover, 10 of the 11 patients
patients with septic shock [14]. For patients with symptomatic who remained hypotensive on high-dose dopamine improved
bradycardia and hypotension who have failed atropine or ex- with the addition of norepinephrine. A subsequent prospective,
ternal pacing, epinephrine may be used to stabilize the patient nonrandomized, observational study suggested that in adults
while awaiting more definitive therapy (e.g., transvenous place- with septic shock treated initially with high-dose dopamine or
ment of a temporary or permanent pacemaker) [15]. When used norepinephrine, the use of norepinephrine was associated with
to treat hypotension, epinephrine is given as a continuous in- improved survival [18]. In the setting of sepsis, norepinephrine
fusion starting at a low dose (0.5 to 1.0 g per minute) and improves renal blood flow and urine output [19], although
titrating up to 10 g per minute as needed. Continuous infu- large doses may be required to achieve these effects due to -
sions of epinephrine may cause restlessness, tremor, headache, receptor downregulation [2].
and palpitations. Epinephrine should be avoided in patients Adverse effects of norepinephrine include increased my-
taking -adrenergic antagonists, as unopposed -adrenergic ocardial oxygen consumption causing ischemia and renal and
vasoconstriction may cause severe hypertension and cerebral mesenteric vasoconstriction. Renal ischemia, may be of par-
hemorrhage. ticular concern in patients with hemorrhagic shock. Nore-
pinephrine can also cause necrosis and sloughing at the
site of intravenous injection owing to drug extravasation.
Norepinephrine Norepinephrine is relatively contraindicated in patients with
hypovolemia. As previously discussed, the overall effect of
Norepinephrine is an endogenous catecholamine that is a norepinephrine on gut mucosal oxygenation in septic patients
potent 1 - and 1 -adrenergic agonist, with little 2 activity. compares favorably with that of high-dose dopamine.
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Chapter 32: Approach to the Patient with Hypotension and Hemodynamic Instability 311

chronotropic effects (Fig. 32.2). Isoproterenol also increases


Phenylephrine heart rate by increasing atrioventricular nodal conduction. Sys-
temic and pulmonary vascular resistances decrease owing to
Phenylephrine is a synthetic sympathomimetic amine that selec- 2 -mediated vasodilation in skeletal muscle and pulmonary
tively stimulates 1 -adrenergic receptors. When administered vasculature, respectively. Reduced peripheral resistance typi-
intravenously, phenylephrine causes dose-dependent arterial cally causes a fall in mean arterial and diastolic blood pressure,
vasoconstriction and increases peripheral vascular resistance. whereas systolic blood pressure is unchanged or rises mod-
As blood pressure rises, activation of vagal reflexes causes slow- estly owing to increased cardiac output. Coronary blood flow
ing of the heart rate. remains unchanged, which in the face of increased myocar-
Phenylephrine, infused at 40 to 180 g per minute, is com- dial oxygen demand can produce ischemia in patients with is-
monly used in the management of anesthesia-induced hypoten- chemic heart disease. In addition, stimulation of myocardial
sion [20,21] and hyperdynamic septic shock. Its rapid onset of 2 -receptors can cause arrhythmias via increased dispersion of
action, short duration, and primary vascular effects make it an repolarization [27].
ideal agent for treating hemodynamically unstable patients in Stimulation of -adrenergic receptors in the heart by iso-
the intensive care setting. However, there are few data regard- proterenol increases the risk of excessive tachycardia, tachy-
ing its relative efficacy compared with older vasopressors such arrhythmias, and myocardial ischemia. Given the likelihood
as norepinephrine and dopamine. In one small study of fluid- of toxicity and the availability of alternative drugs, isopro-
resuscitated patients with septic shock, the addition of phenyle- terenol is no longer used as an inotropic agent; rather, its use
phrine to dobutamine or dopamine increased mean arterial is limited to the temporary treatment of hemodynamically sig-
pressure and systemic vascular resistance without a change in nificant bradycardia unresponsive to atropine while awaiting
heart rate [22]. In addition, urine output improved while serum more definitive treatment with an external or transvenous pace-
creatinine remained stable. The absence of -adrenergic ago- maker. The starting infusion rate for isoproterenol is 1 g per
nist activity at usual doses (phenylephrine activates receptors minute, and this can be titrated up to 10 g per minute to
only at much higher doses) makes phenylephrine an attrac- achieve the desired response (e.g., for bradycardia, titrated to
tive agent for the management of hypotension in clinical situa- a heart rate of 60 beats per minute or higher, depending on the
tions where tachycardia or tachyarrhythmias, or both, limit the blood pressure response). Other uses for isoproterenol include
use of other agents [2]. As with other vasopressors, high-dose chemical overdrive pacing for torsades de pointes refractory
phenylephrine may cause excessive vasoconstriction. In addi- to magnesium [28], and temporary inotropic and chronotropic
tion, patients with poor ventricular function may not tolerate support after cardiac transplantation [29]. Side effects of iso-
the increased afterload induced by 1 -stimulation [22]. Com- proterenol include palpitations, headache, flushing, and rarely
pared to epinephrine and norepinephrine, phenylephrine is less paradoxical bradycardia [30].
likely to decrease microcirculatory blood flow in the gastroin-
testinal tract [23].
Dobutamine
Ephedrine Dobutamine is a synthetic sympathomimetic amine that was
derived from isoproterenol in an attempt to create a less ar-
Ephedrine is a naturally occurring sympathomimetic amine de- rhythmogenic positive inotrope with minimal vascular effects.
rived from plants. Its pharmacologic action results from di- Although initially thought to be a selective 1 -adrenergic ag-
rect nonselective activation of adrenergic receptors, as well as onist, its mechanism of action appears to be more complex.
stimulation of norepinephrine release from storage sites. Al- Dobutamine is available for clinical use as a mixture of two
though ephedrine is less potent and longer acting (half-life, 3 enantiomeric forms with different pharmacologic properties.
to 6 hours) than epinephrine, its hemodynamic profile is similar Ruffolo et al. [31] showed that although both stereoisomers
and includes cardiac stimulation and peripheral vasoconstric- are nonselective -agonists, the positive isomer is several times
tion. more potent. In addition, the two isomers have opposing ef-
Ephedrine is rarely used in the critical care setting except fects on -adrenergic receptors: the positive isomer is an -
in the temporary treatment of hypotension induced by spinal antagonist and the negative isomer is a potent 1 -agonist. The
anesthesia [20]. Ephedrine does not appear to compromise overall effect of the racemic mixture is potent nonselective -
uterine blood flow and is considered by some to be the va- and mild -adrenergic stimulation [31].
sopressor of choice in the treatment of anesthesia-induced hy- Cardiac contractile force is enhanced by 1 - and -
potension in the obstetric patient [24]. However, prophylactic adrenergic stimulation. Heart rate may also increase, but to a
use in pregnant woman undergoing Caesarian section is not lesser extent than occurs with isoproterenol or dopamine (Fig.
recommended as it may cause hypertension and tachycardia 32.1). In contrast to dopamine, dobutamine decreases cardiac
[25]. Ephedrine can be administered in doses of 10 to 25 mg, filling pressures, making it a preferred agent in the treatment of
given as an intravenous bolus every 5 to 10 minutes, with the patients with acute decompensated heart failure [32]. Systemic
total dose not to exceed 150 mg in 24 hours. In healthy women vascular resistance is modestly reduced or may remain un-
undergoing elective cesarean delivery that develop hypoten- changed, as 1 -mediated vasoconstriction is counterbalanced
sion, pharmacogenomic data suggests that 2 -adrenoceptor by 2 -mediated vasodilation and reflex withdrawal of sympa-
genotype may affect dose requirements [26]. Adverse effects thetic tone that typically occurs in response to increased cardiac
of ephedrine include myocardial ischemia and excessive vaso- output. Dobutamine has no effect on dopaminergic receptors;
constriction. however, renal blood flow often increases in proportion to the
increase in cardiac output [33].
Dobutamine, by itself or in combination with other vasoac-
Isoproterenol tive drugs, is useful in the temporary support of myocardial
function in patients with hypotension and poor end-organ per-
Isoproterenol is a synthetic sympathomimetic amine with po- fusion, including those with acute decompensated heart failure
tent nonselective -adrenergic activity and little effect on - as well as patients with concomitant septic shock and depressed
adrenergic receptors. Its major cardiovascular effect is in- cardiac function. In patients with cardiogenic shock, the ef-
creased cardiac output owing to direct positive inotropic and fect of dobutamine on systemic vascular resistance and blood
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312 Section III: Cardiovascular Problems and Coronary Care

pressure is difficult to predict. Therefore, when used in this set- TA B L E 3 2 . 2


ting, it is often administered in combination with dopamine
[7]. SUMMARY OF ADVANCES IN THE MANAGEMENT OF
Dobutamine is generally initiated at an infusion rate of 2 g HYPOTENSION
per kg per minute and can be titrated up to 15 g per kg per
minute or higher to achieve the desired hemodynamic or clini- Vasopressin improves blood pressure in patients with sepsis
cal effects, or both. Side effects that may limit dose titration in- [37] or vasodilatory shock after cardiopulmonary bypass
clude increased heart rate and exacerbation of supraventricular [38].
and ventricular arrhythmias. As with other positive inotropic Methylene blue is effective for refractory hypotension
agents, increased myocardial oxygen consumption can worsen following cardiopulmonary bypass [53] and may be useful in
cardiac ischemia, and short-term dobutamine therapy has been preventing vasoplegia in high-risk patients [54].
associated with excess mortality [34]. Although systolic and Recombinant human activated protein C (drotrecogin alfa
mean arterial blood pressures typically increase, hypotension activated) is indicated for severe sepsis (Apache II score
may occur if dobutamine is administered to a volume-depleted >25) in the absence of bleeding [2,5557].
patient. Some patients with advanced heart failure may be re- Stress-dose steroids improve hemodynamics and may reduce
sistant to dobutamine owing to -receptor hyporesponsiveness mortality in septic shock if adrenocortical insufficiency is
or may develop tolerance after several days of a continuous in- present [62]. Doses of hydrocortisone should not exceed
fusion [35]. Chronic dobutamine therapy may also cause an 200300 mg/day [2].
eosinophilic or hypersensitivity myocarditis [36], leading to
further hemodynamic deterioration.

U per minute) or norepinephrine (5 to 15 g per minute) in ad-


dition to open-label vasopressors. After 28 days, there was no
Vasopressin significant difference in mortality rates between the vasopressin
and norepinephrine groups (35.4% and 39.3%, respectively;
Arginine vasopressin, an antidiuretic hormone, has emerged p = 0.26) (Fig. 32.3). However, in patients with less severe sep-
as a potential alternative to adrenergic vasopressors for the tic shock (prospectively defined as those receiving treatment
treatment of refractory vasodilatory shock. The mechanism of with less than 15 g per minute of norepinephrine), mortal-
action of vasopressin has not been fully elucidated, but likely ity was lower in the vasopressin group (26.5% vs. 35.7%,
involves binding to V1 receptors on vascular smooth muscle p = 0.05).
cells. Although it has minimal pressor activity in normal sub- Vasopressin may also be effective in the treatment of cardiac
jects, vasopressin has been shown to improve blood pressure arrest unresponsive to epinephrine and defibrillation [40]. Re-
in patients with sepsis [37] and in patients with vasodilatory vised guidelines for advanced cardiovascular life support rec-
shock after cardiopulmonary bypass [38] (Table 32.2). In these ommend vasopressin as an alternative to epinephrine for the
initial studies, vasopressin was initiated at a dose of 0.1 U treatment of adult shock-refractory ventricular fibrillation, as
per minute; for subjects maintaining a mean arterial pressure well as an adjunctive agent in the treatment of patients with
greater than 70 mm Hg, vasopressin was tapered to 0.01 U per vasodilatory shock, such as septic shock or sepsis syndrome,
minute and then discontinued. Notably, many patients in these refractory to standard therapy [5]. A meta-analysis of cardiac
studies were poorly responsive to intravenous catecholamine arrest trials demonstrated no significant differences between
support and had inappropriately low vasopressin levels before vasopressin and epinephrine groups in failure of return of spon-
treatment consistent with a defect in baroreflex-mediated va- taneous circulation, death within 24 hours, or death before
sopressin secretion. It remains unclear, however, whether the hospital discharge [41]. In a randomized clinical trial of 2,894
benefits of vasopressin are confined to patients with relative patients with out-of-hospital cardiac arrest receiving advanced
vasopressin deficiency, hypersensitivity, or both. cardiac life support, the combination of vasopressin (40 IU)
Russell et al. [39] randomized 778 patients with septic shock and epinephrine (1 mg) did not improve outcomes compared
who were receiving a minimum of 5 g per minute of nore- to epinephrine alone: return of spontaneous circulation, 28.6%
pinephrine to receive either low-dose vasopressin (0.01 to 0.03 versus 29.5%; survival to hospital admission, 20.7% versus

1.0
P = .27 P = .10
0.9 at day 28 at day 90
Probability of Survival

0.8

0.7

0.6 Vasopressin

0.5
Norepinephrine
0.4
FIGURE 32.3. KaplanMeier survival curves for pa-
0.0 tients with septic shock randomized to vasopressin (solid
0 10 20 30 40 50 60 70 80 90 line) or norepinephrine (dashed line). The dashed vertical
Days since Initiation of the Study Drug line marks day 28. P values are calculated with use of
the log rank test. [From Russell JA, Walley KR, Singer J,
No. at Risk et al: Vasopressin versus norepinephrine infusion in pa-
Vasopressin 397 301 272 249 240 234 232 230 226 220 tients with septic shock. N Engl J Med 358:877887,
Norepinephrine 382 289 247 230 212 205 200 194 193 191 2008, with permission.]
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Chapter 32: Approach to the Patient with Hypotension and Hemodynamic Instability 313

21.3%; and survival to hospital discharge, 1.7% versus 2.3%; blue has also been used successfully to treat refractory hypoten-
respectively [42]. In the setting of vasodilatory shock, vaso- sion in patients with vasoplegia following cardiopulmonary by-
pressin can be administered as a continuous infusion at 0.01 pass (Table 32.2) [53], and may be used to prevent vasoplegia
to 0.05 U per minute. Potential adverse effects of vasopressin in high-risk cardiac surgical patients [54]. However, the over-
include excess vasoconstriction causing end-organ ischemia in- all safety and efficacy of NO inhibition remains unproven. A
cluding myocardial ischemia and hyponatremia. Cardiac out- large, randomized, placebo-controlled trial of the NO synthase
put may also worsen owing to increased afterload. inhibitor 546C88 in sepsis was stopped prematurely due to ex-
Terlipressin is a synthetic long-acting analog of vasopressin cess mortality at 28 days (59% vs. 49%, p < 0.001) in the
that is currently undergoing clinical investigation [43]. In a active treatment arm [51]. As with adrenergic agents, lack of
recent pilot study of patients with septic shock despite ade- selectivity may have contributed to undesirable effects. More
quate volume resuscitation, a continuous infusion of low-dose selective NO inhibitors are currently under investigation.
terlipressin (1.3 g per kg per hour) was effective in revers- Another novel agent that has recently been approved for the
ing arterial hypotension and reducing catecholamine require- treatment of patients with severe sepsis is recombinant human
ments [44]. Compared with vasopressin or norepinephrine, ter- activated protein C (drotrecogin alfa activated) [55]. In the Re-
lipressin was associated with less rebound hypotension upon combinant Human Activated Protein C Worldwide Evaluation
discontinuation. Adverse effects associated with terlipressin in- in Severe Sepsis study, 1,690 patients with systemic inflamma-
clude hypertension, bradycardia, skin pallor, and reduction in tion and organ failure owing to acute infection (71% of whom
platelet count. presented with shock) were randomized to receive drotrecogin
alfa activated or placebo as a continuous infusion for 4 days
[56]. Drotrecogin alfa activated reduced all-cause mortality by
Adjunctive and Investigational Agents 19%, but tended to increase the risk of serious bleeding. Based
on this study, drotrecogin alfa activated is recommended for
In addition to the agents discussed previously, the phosphodi- the treatment of patients with severe sepsis and high risk of
esterase inhibitor milrinone is commonly used in the manage- death (Apache II score greater than 25) (Table 32.2). The stan-
ment of acute decompensated heart failure. Milrinone increases dard intravenous dosing is 24 g per kg per hour for 96 hours,
cardiac contractility by directly inhibiting the breakdown of at a cost of approximately $6,000. In a subsequent study of
cyclic adenosine monophosphate, resulting in an increase in in- patients with severe sepsis and low risk of death (Apache II
tracellular calcium [45]. In addition, phosphodiesterase inhibi- score less than or equal to 25), there was no beneficial effect
tion in vascular smooth muscle causes systemic and pulmonary of drotrecogin alfa activated on either in-hospital or 28-day
vasodilation [46]. Because milrinone does not require binding mortality [57]. The risk of serious bleeding was higher (2.4%
to adrenergic receptors to exert its effects, it is particularly use- vs. 1.2%, p = 0.02) in the drotrecogin alfa activated group.
ful in the treatment of patients taking -adrenergic antagonists A randomized controlled study of drotrecogin alfa activated in
or those with advanced heart failure that may be resistant to children with severe sepsis also showed no benefit [58]. The 28-
-agonist stimulation with dobutamine [35]. Milrinone is gen- day mortality rates were 17.2% and 17.5% in the drotrecogin
erally administered as an intravenous loading dose (50 g per alfa activated and placebo groups, respectively ( p = 0.93).
kg), followed by a continuous infusion at doses ranging from Several hormones including cortisol and thyroxine are
0.25 to 0.75 g per kg per minute. As it is renally excreted, known to play important roles in the maintenance of vascular
milrinone should be dose-adjusted in renal failure; and in all tone, and their absolute or relative deficiency may contribute
patients, milrinone should be titrated cautiously, using inva- to hypotension in the critically ill patient. The adverse effects
sive hemodynamic monitoring. Because it is a potent vasodila- of hypothyroidism (see Chapter 103) and adrenal insufficiency
tor, however, milrinone should be avoided in the treatment of (see Chapter 104) on central and peripheral hemodynamics
patients with frank hypotension and is contraindicated in pa- have been well described. Although routine use of high-dose
tients with severe aortic stenosis. Similarly, the use of levosi- corticosteroids have not been shown to be beneficial in the
mendan [47], a calcium sensitizer with phosphodiesterase and treatment of sepsis, the administration of stress-dose steroids
potassium channel inhibitor properties, may be limited by hy- to patients suspected of having relative impairment of adreno-
potension [48]. In a randomized, double-blind study of 1,327 cortical response may be helpful in restoring normal hemody-
patients with acute decompensated heart failure, intravenous namics and improving outcomes.
levosimendan showed no benefit compared to dobutamine in In the 1990s, three small trials in patients with septic shock
reducing all-cause mortality at 180 days (26% vs. 28%, re- demonstrated decreased duration of shock with steroid treat-
spectively; hazard ratio, 0.91; 95% confidence interval, 0.74 to ment [5961]. Subsequently, Annane et al. [62] randomized
1.13; p = 0.40), and increased the incidence of atrial fibrilla- 300 patients with septic shock to receive hydrocortisone (50 mg
tion [49]. Although approved for use in Europe, levosimendan intravenous bolus every 6 hours) and fludrocortisone (50 g
remains investigational in the United States. by mouth once daily) or matching placebos for 7 days. Patients
With the exception of vasopressin, all currently available were enrolled after undergoing a short corticotropin stimula-
vasopressors exert their action through stimulation of - tion test. In the 229 nonresponders to corticotropin (i.e., with
adrenergic receptors. This approach is often associated with relative adrenal insufficiency), treatment with corticosteroids
worsening splanchnic perfusion, and in some patients may increased vasopressor withdrawal (57% vs. 40%, p = 0.001)
prove ineffective in restoring mean arterial pressure. Evidence and decreased mortality (53% vs. 63%, p = 0.02) at 28 days.
of the central role of endothelium-derived nitric oxide (NO) There were no differences in outcomes between steroid and
in mediating vasodilation [50] led to the development of sub- placebo groups in the corticotropin responders. Although this
stances that interfere with NO production or activity. Several trial was criticized on both methodologic and clinical grounds,
investigators have shown that analogs of l-arginine, the syn- a subsequent meta-analysis (Fig. 32.4) showed that a 5- to 7-
thetic precursor of NO, can competitively inhibit the enzyme day course of physiologic hydrocortisone doses increased sur-
NO synthase, thereby decreasing NO production and increas- vival in patients with vasopressor-dependent septic shock [63].
ing mean arterial pressure in patients with septic shock [51]. In a more recent study, 499 patients with septic shock who
Others have shown that inhibition of guanylate cyclase, the tar- remained hypotensive after fluid and vasopressor resuscitation
get enzyme of NO, with methylene blue is effective in increasing were randomized to receive 50 mg of intravenous hydrocorti-
mean arterial pressure, reducing the need for vasopressors and sone or placebo every 6 hours for 5 days [64]. At 28 days, there
maintaining oxygen transport in septic shock [52]. Methylene was no significant difference in mortality between patients in
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314 Section III: Cardiovascular Problems and Coronary Care

Relative Shock
Reversal
Study, Year (Reference) Benefit (95% Cl)

Bollaert et al., 1998 (59) 3.24 (1.507.01)


Briegel et al., 1999 (60) 1.13 (0.861.46)

Chawla et al., 1999 (61) 2.09 (1.143.83)

0.14 0.37 1.00 2.72 7.39


Relative Benefit
Hazard Ratio for
Shock Reversal FIGURE 32.4. The relative benefit and hazard
Study, Year (Reference) (95% Cl) ratio (with 95% CI) of shock reversal for sepsis
trials published after 1997. In three of the four
Annane et al., 2002 (62) 1.54 (1.102.16) trials, the discontinuation of vasopressor ther-
2 1 0 1 2 apy with steroid treatment was significantly im-
Hazard Ratio proved. [From Minneci PC, Deans KJ, Banks SM,
et al: Meta-analysis: the effect of steroids on sur-
No
Harm Benefit vival and shock during sepsis depends on the dose.
Effect
Ann Intern Med 141:4756, 2004, with permis-
Shock Reversal sion.]

the two study groups whose plasma cortisol levels did not vasopressor agents. Although dopamine in moderate to high
rise appropriately after administration of corticotropin (39.2% doses can provide both positive inotropic and vasopressor ef-
vs. 36.1% in the hydrocortisone and placebo groups, respec- fects, arrhythmias may be provoked (see discussion of SOAP
tively; p = 0.69) or between those who had a response to corti- II later). For severe hypotension (systolic blood pressure less
cotropin (28.8% vs. 28.7%, respectively; p = 1.00) (Fig. 32.5). than 70 mm Hg), a more potent 1 -adrenergic agonist such as
As discussed previously, correction of relative vasopressin de- norepinephrine should be considered.
ficiency is an alternative or adjunctive therapeutic strategy in For the hypotensive patient with significant cardiac pump
refractory shock. dysfunction (cardiac index less than 2.2 L per minute per m2
associated with end-organ dysfunction), dobutamine should
be considered. Milrinone is often not tolerated in this situation
Calcium due to its vasodilating properties. With frank cardiogenic shock
and concomitant vasoplegia, a drug with pressor action is usu-
The routine use of intravenous calcium has been shown to have ally needed. In this setting, vasopressin and norepinephrine can
no benefit in the setting of cardiac arrest and may be detrimen- be used in combination with dobutamine. Rarely, epinephrine
tal by causing cellular injury [4]. Indications for acute calcium may be required. In patients with septic shock and related my-
administration in the hypotensive patient include correction ocardial dysfunction, dobutamine can be added for additional
of clinically significant hyperkalemia (e.g., with acute kidney inotropic support. Although dopamine is also often consid-
injury) or hypocalcemia (e.g., following multiple blood trans- ered in such situations for its combined inotropic and pressor
fusions) and as an antidote to calcium channel blocker or beta- properties there has been recent concern of increased mortality
blocker overdose [65]. Calcium chloride (100 mg per mL in a when compared to norepinephrine in a subgroup of patients
10-mL vial) is usually given as a slow intravenous push of 5 with cardiogenic shock in the recent SOAP II trial (see later).
to 10 mL, and may be repeated as needed. Rapid intravenous Given the superior potency of norepinephrine and evidence
administration of calcium may cause bradycardia or asystole of worsening splanchnic perfusion with high-dose dopamine,
particularly in patients receiving digoxin. In critically ill pa- norepinephrine is emerging as the agent of choice for vasodila-
tients, ionized calcium rather than total calcium concentration tory shock in sepsis [16]. Although in the landmark Sepsis Oc-
should be followed. currence in Acutely Ill Patients (SOAP) II trial, there was no
difference between the initial use of dopamine versus nore-
pinephrine for shock in 28 day all-cause mortality, dopamine
CHOOSING AN AGENT was associated with more adverse events, particularly atrial
fibrillation [66]. Dopamine may be used as an alternate agent
There are few large, randomized, well-controlled studies to or in cases in which positive inotropic effects are desirable.
guide the pharmacologic management of hypotension. The use Current experience with phenylephrine is insufficient to assess
of vasopressors and positive inotropes is generally based on its efficacy relative to older agents, although its peripheral se-
data from animal studies and small, often poorly controlled lectivity and lack of positive chronotropic effects make it a
clinical trials. Useful consensus recommendations can be found theoretically useful agent in cases in which tachycardia, tach-
in the recently revised Advanced Cardiovascular Life Support yarrhythmias, or both limit the use of other drugs. Epinephrine
guidelines [5] and the international guidelines for management is the least selective of the catecholamines and is occasionally
of severe sepsis and septic shock updated in 2008 [2]. added for refractory septic shock. Vasopressin is emerging as
The selection of the appropriate vasoactive agent can be an alternative to adrenergic agents, but its use for hypotension
individualized with attention to the known or suspected un- may be limited to patients with hemodynamic collapse that
derlying cause of hypotension (Table 32.3). However, the clin- is resistant to adequate fluid resuscitation and high-dose con-
ician is commonly faced with a patient who presents with ventional vasopressors. For patients at high risk of death from
life-threatening hypotension of unknown etiology. In this set- sepsis (APACHE II score greater than 25) and low bleeding
ting, it may be necessary to initiate a vasopressor as a temporiz- risk, recombinant human activated protein C is recommended
ing measure even before the adequacy of intravascular volume [2,55]. For patients refractory to multiple pressors, including
repletion can be ensured. Consensus guidelines and expert pan- those status post cardiopulmonary bypass, a trial of methylene
els recommend both dopamine and norepinephrine as first-line blue should be considered [52,53].
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Chapter 32: Approach to the Patient with Hypotension and Hemodynamic Instability 315

A No Response to Corticotropin
100
Probability of Survival (%)

75 Placebo

Hydrocortisone
50

25

0
0 5 10 15 20 25 30
Day

B Response to Corticotropin
100 Hydrocortisone
Probability of Survival (%)

Placebo
75

50

25

0
0 5 10 15 20 25 30
Day

C All Patients
100
Probability of Survival (%)

75 Placebo
FIGURE 32.5. Shown are KaplanMeier
Hydrocortisone curves for survival at 28 days comparing
50
patients with septic shock who received
hydrocortisone versus placebo. There was no
difference among patients who did not have
25 a response to a corticotropin test (Panel A),
those who had a response to corticotropin
(Panel B) and all patients randomized (Panel
0 C). [From Sprung CL, Annane D, Keh D,
0 5 10 15 20 25 30 et al: Hydrocortisone therapy for patients
with septic shock. N Engl J Med 358:
Day 111124, 2008, with permission.]

regional perfusion in addition to the mean arterial pressure to


CLINICAL USE OF guide therapy. Altered mental status, oliguria, and cool skin are
VASOACTIVE DRUGS important clinical signs of poor perfusion, but are somewhat
nonspecific. The clinical use of mixed venous oxygen saturation
In the volume-resuscitated patient with persistent hypotension, and serum lactate level, as well as intramucosal pH monitor-
vasoactive medications are administered with the goal of im- ing by gastric tonometry remains unproven [2]. Although some
proving arterial pressure while avoiding myocardial ischemia, clinicians have advocated achieving supranormal levels of
arrhythmias, and excess vasoconstriction. Although a mean ar- oxygen delivery in the treatment of critically ill patients, this
terial blood pressure of greater than 60 mm Hg is usually ad- approach is controversial [68], and adverse effects of hyperoxia
equate to maintain autoregulatory blood flow to vital organs have been demonstrated on coronary blood flow and myocar-
[67], some patients may require considerably higher pressures. dial function in patients with coronary artery disease [69] and
Therefore, it is essential to use other indicators of global and heart failure [70], respectively. A meta-analysis in critically ill
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316 Section III: Cardiovascular Problems and Coronary Care

TA B L E 3 2 . 3
HEMODYNAMIC PROFILES OF SELECTED CAUSES OF HYPOTENSION AND COMMONLY USED
FIRST-LINE AGENTS

Pulmonary Systemic
Cause of capillary Cardiac vascular Preferred
hypotension wedge pressure output resistance agent(s)

Unknown ? ? ? Dopamine
Hypovolemia Nonea
Acute decompensated heart failure Dopamine, dobutamine
Cardiogenic shock Dopamine
Hyperdynamic sepsis Norepinephrine, dopamine
Sepsis with depressed cardiac function ? Dopamine, norepinephrine plus dobutamine
Anaphylaxis ? ? Epinephrine
Anesthesia-induced hypotension ? ? Phenylephrine, ephedrineb
a
Volume resuscitation with intravenous fluids and/or blood products recommended.
b
For obstetric patients.

patients found that various approaches to hemodynamic op- phentolamine, 5 to 10 mg, diluted in 10 to 15 mL of saline)
timization reduced mortality when patients were treated early can be infiltrated into the area to limit local vasoconstriction
to achieve hemodynamic goals before the development of or- and tissue necrosis.
gan failure and when therapy produced differences in oxygen With few exceptions, the drugs discussed in this chapter
delivery [71]. are short-acting agents with rapid onset and offset of ac-
Vasopressors and positive inotropes are powerful drugs with tion. They are generally initiated without a bolus and can be
considerable potential for toxicity. Diligent monitoring and titrated frequently. Abrupt lowering or discontinuation of va-
careful adjustment of medications based on changes in clinical soactive drugs should be avoided to prevent rebound hypoten-
status are essential. Patients should be treated in an intensive sion. Common dose ranges are provided in Table 32.1, but
care setting with continuous monitoring of cardiac rhythm, there may be considerable variation in the dose required to re-
urine output, and arterial oxygenation. Fluid resuscitation and store adequate hemodynamics. Furthermore, an individual pa-
careful attention to intravascular volume are paramount, as tients response to an agent may diminish with time owing to
up to 50% of patients with hypotension related to sepsis may several mechanisms, including adrenergic receptor desensitiza-
stabilize with fluids alone [2]. Moreover, the administration of tion.
vasopressors to intravascularly depleted patients can worsen Critically ill patients in the intensive care unit are generally
end-organ perfusion. The routine use of pulmonary artery treated with multiple drugs in addition to vasoactive agents
catheters in this setting remains unproven, as overaggressive (e.g., other cardiovascular medications, antibiotics). Careful
treatment may increase the risk of adverse events [72]. How- attention should be paid to potential drugdrug interactions,
ever, a randomized trial demonstrated that early goal-directed as they can significantly alter the response to a given sympath-
therapy, using a central venous catheter capable of measuring omimetic amine. For example, prior or current treatment with
oxygen saturation, improved outcomes in patients with sep- a -adrenergic antagonist can cause resistance to the action
tic shock [73]. In patients who do not respond adequately to of dobutamine or other -adrenergic agonists. The adminis-
initial fluid boluses and brief infusion of vasopressors, inva- tration of less-selective drugs (e.g., norepinephrine) to a pa-
sive hemodynamic monitoring may aid in optimizing filling tient receiving chronic beta-blockade can result in unopposed
pressures and selecting the appropriate vasoactive agent. Intra- -adrenergic stimulation. Another well-described interaction
arterial cannulation and direct monitoring of blood pressure is is the exaggerated response to some catecholamines in individ-
suggested during prolonged vasopressor use. Drugs should be uals taking monoamine oxidase inhibitors. The starting dose
administered through central venous catheters via volumetric for these patients should be less than 10% of the usual dose
infusion pumps that deliver precise flow rates. In the event of [1]. Intensive care unit rounding with a dedicated pharmacist
vasopressor extravasation, an 1 -adrenergic antagonist (e.g., is recommended.

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318 Section III: Cardiovascular Problems and Coronary Care

CHAPTER 33 MANAGEMENT OF
ADVANCED HEART FAILURE
G. WILLIAM DEC

Advanced heart failure accounts for a small minority (approx- recognized that a variety of etiologies including pulmonary em-
imately 10%) of patients with chronic disease. It is generally bolism, acute coronary syndromes, and sepsis may also lead to
defined as persistent New York Heart Association functional markedly elevated BNP [7].
class IIIB or IV symptoms that limit daily activities and oc- Renal dysfunction has recently been recognized as an ex-
cur despite adequate pharmacologic treatment (see later) and tremely powerful predictor of heart failure outcome. Deteri-
is usually associated with a left ventricular ejection fraction oration in renal function may result from diminished cardiac
below 30% [1]. Patients with advanced heart failure typically output and a corresponding reduction in glomerular filtration
have experienced one or more hospitalizations for decompen- rate, alterations in the distribution of cardiac output, intrarenal
sated heart failure within the previous year. vasoregulation, alterations in circulatory volume, more intense
neurohormonal activation, and/or the nephrotoxic effects of
medications administered during hospitalization [8]. The pres-
ence of chronic renal insufficiency, defined as a serum creatinine
PROGNOSTIC FEATURES >1.4 mg/dL for women and >1.5 mg/dL for men, predicts an
increased risk of death (risk ratio = 1.43) [8]. Unfortunately,
More than 50 variables have been examined in univariate and approximately 25% of hospitalized patients with decompen-
multivariate models and shown to predict prognosis in ad- sated heart failure will exhibit deterioration in renal function
vanced heart failure populations. No single study has assessed despite appropriate medical therapy [9]. In these hospitalized
all, or even most, of these predictors simultaneously and it is patients, a rise in serum creatinine of only 0.1 to 0.5 mg/dL is as-
therefore impossible to rank prognostic features strictly based sociated with a longer length of hospital stay and increased in-
on their level of importance. Nonetheless, several features ap- hospital mortality [9]. This constellation of poorly understood
pear repeatedly in the published literature (Table 33.1). Eich- physiologic mechanisms has been termed the cardiorenal syn-
horn identified plasma norepinephrine level, B-type natriuretic drome and its optimal management remains to be defined.
peptide (BNP) level, left ventricular ejection fraction, peak oxy- Thus, a variety of demographic, clinical, hemodynamic
gen uptake on cardiopulmonary exercise testing, advanced age, and laboratory findings help to accurately characterize pa-
and a history of symptomatic ventricular arrhythmias or sud- tients with advanced heart failure at increased risk of adverse
den cardiac death as the most important predictors of outcome events during hospitalization. Proper identification of these pa-
[2]. tients should lead to improved management strategies. Her-
Functional capacity, as assessed by the New York Heart clas- nandez, et al. have reported that patients with heart failure
sification remains among the most useful outcome predictors undergoing major noncardiac surgical procedures experience
in advanced heart failure. One year mortality rates range from substantially increased morbidity compared to patients with
<5% for Class I, 10% to 15% for Class II, 20% to 30% for ischemic heart disease or an age-matched population [10]. Af-
Class III, with Class IV patients experiencing rates of 30% to ter adjusting for demographic characteristics, type of surgery,
70% depending on their response to therapy [2]. Although left
ventricular ejection fraction (LVEF) is a consistent predictor
of outcome in a heterogeneous population of patients whose
TA B L E 3 3 . 1
left ventricular ejection fractions range from 10% to 50% [2],
this parameter correlates very poorly with symptoms or day-to- PREDICTORS OF PROGNOSIS IN CHRONIC
day functional capacity and loses much of its predictive accu- HEART FAILURE
racy among patients with advanced symptoms [3]. In advanced
heart failure, small variations in markedly depressed LVEF (i.e., Demographic Advanced age, sex, ischemic etiology
between 10% and 20%) have little bearing on symptoms or Symptoms NYHA class IV, syncope
prognosis [2,3]. Signs Chronic S3, right heart failure
Findings on physical examination also predict prognosis Laboratory Na+ , creatinine, anemia, CTR, LVEDD
and should influence treatment during hospitalization. The ECG QRS or QTc prolongation, NSVT, VT
presence of a chronic third heart sound or elevation in jugular Hemodynamic LVEF, PCW, CI
venous pressure establishes more advanced disease and predict Exercise 6-min walk distance, peak VO2
increased long-term mortality [4]. Both moderate-to-severe mi- Neurohormonal PNE, ANP, BNP
tral or tricuspid regurgitation are also associated with increased
symptoms, morbidity, and mortality [5]. ANP, atrial natriuretic peptide; BNP, B-type natriuretic peptide; CI,
Serum B-type natriuretic peptide (BNP) and N-terminal- cardiac index; CTR, cardiothoracic ratio on chest film; LVEDD, left
pro-BNP are increasingly measured in patients with suspected ventricular end-diastolic dimension on echocardiogram; LVEF, left
ventricular ejection fraction; NSVT, nonsustained ventricular
heart failure. Recent data suggest that serial assessment of BNP tachycardia; PCW, pulmonary capillary wedge pressure; PNE, plasma
during hospitalization is useful in predicting postdischarge norepinephrine; VO2 , oxygen consumption on cardiopulmonary
prognosis and suggests that this approach may soon help guide exercise testing; VT, ventricular tachycardia.
heart failure inpatient management [6]. However, it should be
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Chapter 33: Management of Advanced Heart Failure 319

and comorbid conditions, the risk-adjusted operative mortal-


ity (death before discharge or within 30 days of surgery) was Diuretics
11.7% for heart failure patients, 6.6% for ischemic heart dis-
ease patients, and 6.2% for controls. Further, the risk-adjusted Diuretics remain the mainstay for congestive symptoms but
30-day re-admission rates were 20% for the heart failure co- have not been shown to improve survival. Neurohormonal
hort compared with 14% for the ischemic population and 11% activation (as measured by circulating renin, angiotensin, en-
for age-match controls. The presence of a third heart sound dothelin, and BNP) has been shown to acutely decrease during
or signs of overt heart failure clearly identifies patients at in- short-term diuretic therapy administered to lower markedly
creased risk for adverse outcome during noncardiac surgical elevated filling pressures [15]. Two pharmacologic classes of
procedures [11]. Every effort must be made to detect unsus- agents are relevant to acute heart failure management: loop di-
pected heart failure by careful evaluation and to optimize ther- uretics and distal tubular agents (Table 33.2). The loop diuret-
apy before embarking on nonemergent procedures. ics (e.g., furosemide, torsemide, bumetanide, and ethacrynic
Fonarow et al., using the ADHERE registry data on over acid) are the most potent. Some data suggest that torsemide
33,000 hospitalizations has performed the most detailed risk and bumetanide may be more effective than furosemide in ad-
stratification of in-hospital mortality in acute decompensated vanced heart failure, perhaps due to superior absorption from
heart failure [12]. The best single predictor for morality was the gastrointestinal tract in the setting of elevated right-sided
high admission level of blood urea nitrogen (>43 mg/dL), filling pressures [15]. Although once daily dosing of loop di-
followed by an admission systolic blood pressure below 115 uretic is usually effective for outpatient therapy, patients with
mm Hg, and a serum creatinine level >2.75 mg/dL. Using persistent symptoms or those with marked hemodynamic insta-
these three variables, patients could be readily stratified into bility during hospitalization often require dosing two or three
groups at low, intermediate, and high risk for in-hospital mor- times a day to adequately manage volume overload.
tality with rates ranging from 2.1% to 21.9% [12]. Additional Thiazide diuretics such as hydrochlorothiazide and metola-
predictive variables in other studies include troponin release, zone act mainly by inhibiting reabsorption of sodium and chlo-
markedly elevated natriuretic peptide levels, and hyponatremia ride in the distal convoluted tubule of the kidney. Used alone,
[13]. thiazides produce a fairly modest diuresis; these agents are
ineffective when glomerular filtration rate (GFR) falls below
40 ml per minute [15].
PHARMACOLOGICAL Diuretic tolerance is often encountered in patients with ad-
vanced heart failure. Lack of response to diuretic therapy may
MANAGEMENT OF ADVANCED be caused by excessive sodium intake, use of agents that antag-
HEART FAILURE onize their effects (particularly nonsteroidal anti-inflammatory
drugs), worsening renal dysfunction, addition of potentially
Heart failure that persists after correction of potentially re- nephrotoxic agents during hospitalization or compromised re-
versible causes (i.e., anemia, hyperthyroidism, valvular heart nal blood flow due to worsening cardiac function. Combined
disease, myocardial ischemia) should be treated with dietary intravenous loop diuretic plus thiazide creates a synergistic re-
sodium restriction, diuretics for volume overload, vasodila- sponse and should be considered for patients who fail to diurese
tor therapy (particularly angiotensin-converting enzyme (ACE) despite optimal doses of an intravenous loop diuretic alone.
inhibitors or angiotensin receptor antagonists),and a beta- Metolazone is particularly effective when administered with a
adrenergic blocker (Fig. 33.1). Sodium restriction (<4 g per loop diuretic. High-dose furosemide when administered as a
day) is generally indicated for patients with advanced symp- continuous infusion (1 to 10 mg per hour) may also be more
toms [14]. Likewise, most patients with advanced heart failure effective than bolus administration for hospitalized patients
require a 1.5 to 2 L per day fluid restriction. [16].

NYHA
Class
Agent I II III IV

Statins

Diuretics

ACEI or ARB

Beta-blockers

Digoxin
FIGURE 33.1. Standard pharmaco-
Spironolactone logical approach to heart failure based
upon agent and severity of clinical
heart failure symptoms [From Eich-
No proven mortality benefit, horn E: Current pharmacologic treat-
May offer mortality benefit No data for or against
used in symptomatic patients ment of heart failure. Clin Cardiol
Should not be used in this 22:V21V29 (Figure 1), 1999, with
Use for mortality benefit
Class permission.]
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320 Section III: Cardiovascular Problems and Coronary Care

TA B L E 3 3 . 2
INTRAVENOUS DIURETIC REGIMENS FOR TREATING DECOMPENSATED
HEART FAILURE

Drug Initial dose Maximal single dose

Loop diuretics
Furosemide 40 mg 200 mg
Bumetanide 1 mg 48 mg
Torsemide 10 mg 100200 mg
Thiazide diuretics
Chlorothiazide 500 mg 1,000 mg
Synergistic nephron blockade
Chlorothiazide 5001,000 mg + loop diuretics 14 per day
Metolazone 2.510 mg PO + loop diuretic 12 per day
Intravenous infusions
Furosemide 40 mg IV loading dose; then 540 mg/hour infusion
Bumetanide 12 mg IV loading dose; then 0.52 mg/hour infusion
Torsemide 20 mg IV loading dose; then 520 mg/hour infusion

IV, intravenous; PO, by mouth.

Elevated vasopressin levels play an important role in medi- therapy since both preload and afterload are elevated in de-
ating fluid retention and contributing to hyponatremia. Short- compensated heart failure. However, in the ICU setting, it may
term treatment with the V2-receptor antagonist, tolvaptan, has sometimes be useful to use nitrates to reduce markedly elevated
been shown to lower filling pressures, enhance diuresis, cor- preload or hydralazine to treat elevated afterload for short pe-
rect hyponatremia, and improve renal function [17]. However, riods of time. ACE inhibitors play a crucial role by altering
tolvaptan had no effect on long-term mortality or heart-failure the vicious cycle of hemodynamic abnormalities and neuro-
related morbidity in a study of over 500 hospitalized with acute hormonal activation that characterize advanced heart failure.
decompensated failure [17]. Thus, the role of this class of agents Randomized, controlled clinical trials have demonstrated the
remains uncertain. beneficial effects of ACE inhibitors on functional capacity, neu-
Ultrafiltration using a venovenous access approach is now rohormonal activation, quality of life, and long-term survival
feasible and potentially useful for acutely lowering elevated in patients with chronic heart failure due to left ventricular
ventricular filling pressures when conventional high-dose com- systolic dysfunction (Table 33.3). There is compelling evidence
bination diuretic therapy fails to produce adequate diuresis. that ACE inhibitor therapy should be prescribed whenever fea-
Small, short-term observational studies suggest improvements sible in all symptomatic heart failure patients. Despite their
in weight loss during hospitalization but have not demon- unequivocal benefits, only 60% to 75% of all heart failure pa-
strated decreased length of stay or better preservation of re- tients currently receive these agents [20]. The elderly and pa-
nal function [18]. The UNLOAD trial randomized 200 pa- tients with advanced heart failure symptoms are least likely to
tients with acute decompensated heart failure to standard receive this therapy [20]. It is especially important to recognize
intravenous diuretics versus ultrafiltration and demonstrated in patients with advanced heart failure that even low doses
greater weight loss at 48 hours in the ultrafiltration cohort of vasodilator treatment confer benefit. Low-dose treatment
[19]. Readmissions for heart failure were also lower at 90 days should be considered for patients with marginal blood pres-
(32% vs. 18%) for the ultrafiltration group. However, no com- sure (i.e., systolic pressure >80 to 90 mm Hg) to permit the
ment was made on overall rehospitalization rates. No differ- subsequent introduction of beta-blockers. An ACE inhibitor
ence in in-hospital or outpatient renal function was observed should be initiated for any patient who experiences a trans-
between treatment groups [19]. Importantly, hemodynamic in- mural myocardial infarction during hospitalization as postin-
stability has been an exclusion criterion in all published studies. farction trials have shown 10% to 27% reduction in all-cause
The latest ACC/AHA practice guidelines recommend ultrafil- mortality and 20% to 50% reduction in the subsequent risk
tration as a class IIA therapeutic option for heart failure that of developing overt heart failure when these agents are begun
remains refractory to conventional diuretic therapy [14]. Addi- following acute infarction [21].
tional prospective controlled trials are needed to establish the Alternative therapy with combination hydralazine and ni-
exact role of this new treat modality. trates should be considered for patients with marginal renal
function (creatinine >2.5 mg per dL) and those with previously
documented intolerance to ACE inhibitors or ARBs. Similar
Vasodilator Therapy hemodynamic goals can be achieved with these agents among
patients with advanced NYHA Class III or IV heart failure
Vasodilators remain a cornerstone of acute and chronic heart [22]. Women appear somewhat less responsive to ACE in-
failure management [14]. Mechanisms of action vary and hibitor therapy than do men [23]. Important racial differences
include a direct effect on venous capacitance vessels (e.g., may also exist in pharmacologic responsiveness to different va-
nitrates), arterioles (e.g., hydralazine), or balanced effects sodilator regimens. Two retrospective analyses from large trials
(sodium nitroprusside, ACE inhibitors, and angiotensin II re- confirmed ACE inhibitor therapy to be less effective in blacks
ceptor blockers [ARBs]). Drugs that produce balanced venous than whites with heart failure of comparable severity [24]. The
and arteriolar dilatation should generally be chosen as first-line African-American Heart Failure trial (A-HeFT) confirmed the
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Chapter 33: Management of Advanced Heart Failure 321

TA B L E 3 3 . 3
INHIBITORS OF THE RENINANGIOTENSINALDOSTERONE SYSTEM AND
BETA-BLOCKERS USED FOR ADVANCED HEART FAILURE DUE TO SYSTOLIC
DYSFUNCTION

Drug Initial dose Maximal dose

ACE inhibitors
Captopril 6.25 mg three times daily 50 mg three times daily
Enalapril 2.5 mg twice daily 20 mg twice daily
Lisinopril 2.5 mg daily 40 mg daily
Fosinopril 5 mg daily 40 mg daily
Ramipril 1.25 mg daily 10 mg daily
Quinapril 5 mg twice daily 20 mg twice daily
Trandolapril 1 mg daily 4 mg daily
Angiotensin receptor blockers
Losartan 25 mg daily 100 mg daily
Valsartan 20 mg twice daily 160 mg twice daily
Candesartan 4 mg daily 32 mg daily
Aldosterone antagonists
Spironolactone 12.5 mg every other day 25 mg twice daily
Eplerenone 25 mg daily 50 mg daily
Beta-adrenergic blockers
Metoprolol XL/CRa 12.5 mg daily 200 mg daily
Carvedilol 3.125 mg twice daily 50 mg twice daily
Bisoprolol 1.25 mg daily 10 mg daily
a
Metoprolol succinate, extended release.

benefit of hydralazine and isosorbide dinitrate in this popu- sound [27]. A prespecified subgroup analysis of patients en-
lation; this combination should be considered when initiating rolled in the Digitalis Investigation Group (DIG) trial provide
therapy for hospitalized black patients [25]. confirmatory evidence that patients with severe heart failure
ARBs are now also considered suitable first-line therapy for (LVEF <25% or CT ratio >0.55) showed the greatest benefit
heart failure patients [14]. These drugs should be selected for [27]. The drug has neutral effects on all-cause and cardiovas-
ACE-inhibitor intolerant, nonAfrican-American patients who cular mortality [27]. As renal function may fluctuate consid-
experience rash or cough with an ACE inhibitor. They can- erably during hospitalization, measurement of serum digoxin
not be used for patients who experience ACE-inhibitorrelated levels is important [28]. Retrospective subgroup analysis has
deterioration in renal function, hypotension, or hypokalemia suggested an increased risk of all-cause mortality among both
[25]. Symptomatic and mortality benefits appear comparable women and men who have digoxin levels >1.0 ng/dL [28].
between ACE inhibitors and ARBs [14]. For patients with ad- Poor renal function, small lean body mass, and elderly patients
vanced heart failure, the addition of a low-dose ARB to stan- are at greatest risk for developing digoxin toxicity during stan-
dard therapy with ACE inhibitor and beta-blocker provides dard maintenance dosing. In addition, a number of commonly
significant morbidity benefit with reduction in recurrent hospi- used drugs including verapamil, flecainide, spironolactone, and
talizations but no mortality benefit [26]. A modest reduction in amiodarone will significantly increase serum digoxin levels. For
maintenance ACE inhibitor dose may be necessary to introduce adult patients with normal renal function, a dosage of 0.25 mg
an ARB in this population. per day is appropriate. For patients at increased risk of tox-
icity, the initial starting dose should be 0.125 mg daily and
up-titrated as necessary to achieve a trough level of 0.5 to 0.9
ng per dL.
Digitalis
Digoxin continues to have an important role in the manage-
ment of patients with advanced NYHA class IIIIV symp- Beta-Adrenergic Blockers
toms [14]. The drug has mild positive inotropic effect on car-
diac muscle, reduces activation of the sympathetic and renin Three distinct classes of beta-blockers are now available for
angiotensin systems, and partially restores the favorable in- clinical use. Propranolol and other first-generation com-
hibitory effects of cardiac baroreceptor function. Short- and pounds such as timolol are nonselective agents with equal
long-term controlled trials have provided unequivocal evi- affinity for 1 and 2 receptors [29]. Metoprolol and bisopro-
dence that chronic digoxin administration increases left ven- lol are cardioselective second-generation compounds that
tricular ejection fraction, improves exercise capacity, decreases block the 1 receptor to a greater extent than the 2 recep-
advanced heart failure symptoms, and reduces heart failure as- tor. Metoprolol is approximately 75-fold more selective for 1
sociated hospitalizations [27]. Post hoc analysis has shown that than 2 receptors while bisoprolol is 120-fold more selective
patients most likely to demonstrate a favorable response had [29]. Labetalol, carvedilol, and bucindolol are third-generation
severe symptoms, greater degrees of left ventricular dysfunc- compounds that block 1 and 2 receptors with almost equal
tion, lower ejection fractions, and the presence of a third heart affinity. These agents also have ancillary properties including
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322 Section III: Cardiovascular Problems and Coronary Care

1 -blockade (labetalol and carvedilol), antioxidant proper-


ties (carvedilol), and intrinsic sympathomimetic activity (ISA) Aldosterone Antagonists
(bucindolol). Specific beta-blockers have been shown to lower
all-cause mortality and decrease heart failure hospitalizations Circulating aldosterone levels are elevated in relationship to
in a variety of randomized controlled trials in patients with heart failure severity, affect prognosis, and contribute to left
NYHA class IIIV symptoms (Table 33.3) [30,31]. The mor- ventricular remodeling following acute myocardial infarction.
tality benefits of beta-blocker therapy in patients with advanced Potential deleterious effects include endothelial dysfunction,
(NYHA class IV) heart failure symptoms have been established. increased oxidative stress, enhanced platelet aggregation, acti-
The Carvedilol Perspective Randomized Cumulative Survival vation of matrix metalloproteinase, and increased sympathetic
(COPERNICUS) trial evaluated patients with severe symptoms activation. The mineralocorticoid receptor antagonist (MRA)
and LVEF <25% [32]. Carvedilol reduced all-cause mortality spironolactone has been shown to reduce mortality in patients
by 35%, the combined risk of death or cardiovascular hospi- with severe heart failure by 30% [36]. Results of the EPHESUS
talization by 27%, and the risk of death or heart failure hospi- trial confirm that eplerenone, a more selective MRA, can also
talization by 31% [32]. Importantly, carvedilol-treated patients reduce morbidity and mortality amongst patients with evidence
spent 40% fewer days in the hospital for acute heart failure de- of systolic dysfunction and heart failure following acute my-
compensation [32]. It is appears that not all beta-blockers have ocardial infarction [37]. The beneficial effects of MRAs appear
equivalent benefits in heart failure. For example, bucindolol, to be independent of their diuretic actions, and likely relate to
a third-generation nonselective beta-blocker with ISA proper- interruption of the downstream effects of aldosterone activa-
ties, was not associated with statistically significant reductions tion.
in overall mortality amongst patients with advanced heart fail- Spironolactone and eplerenone should not be initiated in
ure. As such, unlike ACE inhibitors or ARBs, the specific beta- the ICU setting. Both can be associated with serious hyper-
blockers validated in clinical trials should be prescribed. The kalemia, particularly in the presence of impaired renal func-
effectiveness of these agents appears equal among men and tion or other medications which impair potassium excretion.
women with advanced heart failure [33]. Clinicians should con- They should be considered for addition to the patients medi-
sider initiating carvedilol as first-line therapy, given its broader cal regimen prior to discharge following optimization of other
antiadrenergic effects whenever possible. However, for patients heart failure therapies. Patients who have been receiving these
with marginal blood pressure in whom alpha blockade may be agents should continue taking them during hospitalization un-
deleterious, metoprolol or bisoprolol may be suitable first-line less marked hemodynamic instability, electrolyte disturbances,
agents. or worsening renal function ensue.
A small minority of patients with advanced heart failure
(<10%) are unable to tolerate even the lowest doses dur-
ing initial attempts at drug introduction. Some investigators
are now combining a phosphodiesterase inhibitor (enoximone INTENSIVE CARE MANAGEMENT
or milrinone) with a beta-blocker [34]. Phosphodiesterase- OF ADVANCED HEART
III inhibitors improve hemodynamics and exercise perfor-
mance but increase the risk of exacerbating myocardial is-
FAILURE PATIENTS
chemia and promoting ventricular arrhythmias. Theoretically,
beta-blockers should counteract the ischemic and arrhyth- Compensated Heart Failure States
mic properties of these agents and provide synergistic ben-
efits. Small uncontrolled short-term studies suggest that this A significant number of patients with advanced heart failure
approach may be beneficial in hospitalized patients with re- are hospitalized each year for management of noncardiac ill-
fractory heart failure [34]. Several randomized clinical trials nesses. Several principles apply to the in-hospital management
are now evaluating the safety and efficacy of combination of patients with compensated disease. Every attempt should
therapy. be made to maintain the patient on the medical regimen that
Beta-blocker treatment should be attempted in all patients has provided optimal outpatient stability. Daily weights as well
including those with advanced heart failure. For patients enter- as a fluid restriction should be instituted for patients with ad-
ing the intensive care unit who have not received such therapy, vanced disease. Establishing a baseline weight and maintaining
treatment should be initiated at very low doses and gradually it through diuretic dosing adjustments is critical to prevent an
up-titrated every few days or within 1 week. The usual starting acute decompensation. Diuretics should be switched to intra-
doses are carvedilol 3.125 mg twice daily or metoprolol succi- venous administration whenever questionable oral absorption
nate 6.25 mg twice daily. Beta-blockers should not be initiated (i.e., postoperative state) is expected. Once daily ACE inhibitor
until optimal volume status and hemodynamic stability have or ARB therapy is ideal for outpatient management to enhance
been achieved. compliance; however, if hemodynamic instability is anticipated
The majority of chronic heart failure patients requiring during hospitalization, a temporary switch to a short-acting
hospitalization are already beta-blocker treated. In general, agent (e.g., captopril in place of lisinopril) should be consid-
beta-blockers should not be withdrawn unless bradycardia or ered. Among patients with deteriorating renal function, it may
hemodynamic instability develops, due to the risk of rebound be necessary to withhold the ACE-inhibitor or ARB and tran-
hypertension and tachycardia. Where necessary to facilitate siently substitute hydralazine and nitrates, particularly when
management of acute decompensated heart failure, a 50% re- creatinine exceeds 3.0 mg per dL. Beta-blocker dosing should
duction in the ambulatory dose is often preferable to drug ces- remain unchanged and may require a modest increase if atrial
sation. In a retrospective observational study of more than tachyarrhythmias are encountered in the postoperative state
2,300 patients eligible to receive beta-blocker during hospi- (see later). Serum electrolytes should be followed frequently,
talization, Fonarow et al. demonstrated that continuation of given the potential for electrolyte disarray (e.g., hypokalemia
beta-blocker was associated with a significantly lower risk in or hypomagnesemia) to potentiate atrial and ventricular ar-
propensity-adjusted postdischarge death and rehospitalization rhythmias in vulnerable patients. Despite marked reduction in
rates compared with the absence of beta-blocker [35]. Further, LVEF, the majority of patients who require hospitalization for
beta-blocker withdrawal was associated with a substantially noncardiovascular illness will remain compensated with regard
higher adjusted risk for mortality (hazard ratio: 2:3) compared to their heart failure symptoms employing a continued main-
to continuation of beta-blockade. tenance regimen.
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Chapter 33: Management of Advanced Heart Failure 323

TA B L E 3 3 . 4
Decompensated Heart Failure States
INDICATIONS FOR HEMODYNAMIC MONITORING
Heart failure decompensation is the most common cause for IN DECOMPENSATED HEART FAILURE
hospitalization for patients over 65 years of age. Stevenson
has popularized a 2-minute clinical assessment to ascertain Ongoing congestive symptoms and suspected end-organ
the hemodynamic profiles for heart failure patients (Fig. 33.2) hypoperfusion
[23,38]. Patients are characterized in 2 2 fashion accord- Narrow pulse pressure Cool extremities
ing to the presence or absence of congestion and low perfusion Declining renal function Hypotension on ACE or ARB
on physical examination [23]. The clinical profiles thus defined Mental confusion Progressive hyponatremia
have been shown to correlate reasonably well with direct hemo-
Heart failure and other medical comorbidities
dynamic measurements of filling pressure and cardiac output
Cardiac: unstable angina pectoris; stenotic valvular
and are correlated with prognosis following hospital discharge
lesions, hypertrophic cardiomyopathy
[23]. Warm and dry patients have normal resting hemody-
Noncardiac: severe obstructive or restrictive
namics and are well compensated. For these patients, other po-
pulmonary disease, advanced renal disease, sepsis
tential etiologies for dyspnea or fatigue should be considered.
The majority (70% to 80%) of patients admitted with worsen- Other situations
ing symptoms fit the warm and wet profile. These individuals Perioperative monitoring to optimize status for high-risk
are volume overloaded but have adequate end-organ perfusion. procedure
The primary treatment goal is thus relief of congestive symp- Symptoms disproportionate to clinical assessment of
toms using intravenous loop diuretics alone or in combination degree of compensation
with a thiazide. Those who fail to respond to escalating doses Uncertain volume status
of intravenous loop diuretics may benefit from a continuous Inability to wean inotropic support
intravenous loop diuretic infusion. The small minority of pa-
tients with refractory volume overload may benefit from con- ACE, angiotensin-converting enzyme; ARB, angiotensin receptor
blocker.
tinuous venovenous hemofiltration (CVVH) or ultrafiltration
[14,38]. Although neurohormonal antagonists including ACE-
inhibitors, ARBs, and beta-blockers should ideally be main-
tained during periods of acute heart failure decompensation,
for patients that are difficult to diurese or hypotensive, down- should be sought. The ESCAPE trial randomized patients with
ward dose adjustment or temporary suspension (particularly of acute decompensation without hemodynamic compromise to
beta-blockers) should be considered. A very small minority of conventional medical management based on physical findings
patients (<5%) fall into the cold and dry profile. These in- and symptoms versus tailored hemodynamic monitoring fol-
dividuals have impaired cardiac output but do not adequately lowing insertion of a pulmonary artery catheter. Somewhat sur-
use the Starling mechanism to increase preload. Judicious hy- prisingly, outcomes did not differ between the two management
dration should be attempted. Patients who fail to demonstrate strategies [39]. Certain high-risk subgroups may, nonetheless,
improvement in end-organ perfusion may require a short-term benefit from short-term hemodynamic monitoring for manage-
infusion of a positive inotropic agent such as dobutamine or ment of acute decompensated heart failure. Principal indica-
milrinone. tions for hemodynamic monitoring with a pulmonary artery
catheter include evidence of worsening end-organ dysfunction,
need for withholding vasoactive medications due to hypoten-
Hemodynamically Guided Therapy sion, heart failure associated with other comorbidities (i.e., un-
Approximately 10% to 15% of patients with advanced heart stable angina or valvular heart disease) or inability to wean
failure will demonstrate marked hemodynamic deterioration positive inotropic support (Table 33.4). Tailored hemody-
on admission (cold and wet profile). These patients have im- namic treatment for refractory heart failure is outlined in
pending cardiogenic shock. Potential causes for acute decom- Table 33.5. Following initial assessment of baseline hemo-
pensation such as recent myocardial infarction, rhythm change, dynamics, intravenous diuretics, vasodilators, or positive in-
worsening valvular disease, or medical/dietary nondiscretion otropes are administered to achieve desired hemodynamic

Evidence of Congestion: Orthopnea Elevated JVP


Third heart sound Edema
Ascites Rales (uncommon)
Abdominojugular reflux
Low Perfusion at Rest?

Congestion at Rest?

No No Yes

Warm and Dry Warm and Wet

Yes Cold and Dry Cold and Wet FIGURE 33.2. Diagram of hemodynamic profiles for
patients presenting with heart failure symptoms. Most
Evidence for Low Perfusion: Narrow pulse pressure ACE-related hypotension patients with advanced heart failure can be classified ac-
Pulsus alternans Declining serum sodium curately in a 2-minute assessment of their physical find-
Cool extremities Worsening renal function ings and symptoms. [From Nohria J, Lewis E, Steven-
Mental confusion son LW: Medical management of advanced heart failure.
JAMA 287:639 (Figure 1), 2002, used with permission.]
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324 Section III: Cardiovascular Problems and Coronary Care

TA B L E 3 3 . 5 complexity needed to readjust oral regimens as the infusions are


weaned [23]. Although positive inotropes should not be rou-
PRINCIPLES OF HEMODYNAMIC TAILORED HEART tinely used for warm and wet patients, these agents can be
FAILURE THERAPY life saving for patients with rapidly progressive hemodynamic
collapse [38]. Patients who present or develop obtundation,
Measure baseline resting hemodynamics (CVP, PAP, PCW, CI, anuria, persistent hypotension, or lactic acidosis may only re-
SVR) spond to inotropic support, which should be continued until
Administer intravenous diuretics, vasodilator (nitroprusside, the cause of cardiac deterioration is determined and definitive
nitroglycerin, or nesiritide) or inotropic agent (milrinone or therapy implemented. Brief inotropic treatment may also be ap-
dobutamine) dosed to achieve specific hemodynamic goals: propriate for patients who develop the cardiorenal syndrome.
Pulmonary capillary wedge pressure <16 mm Hg It should be emphasized, however, that many patients with low
Right atrial pressure <8 mm Hg cardiac output have high systemic vascular resistance that pre-
Cardiac index >2.2 L/min/m2 dictably improves with vasodilator therapy alone, obviating the
Systemic vascular resistance <1,0001,200 dynes/sec/cm5 need for inotropic support [23,38]. In-hospital mortality has
Systolic blood pressure >80 mm Hg also been shown to be lower for nonhemodynamically compro-
Maintain optimal hemodynamics for 2448 hours mised patients treated with intravenous vasodilators compared
Up-titration of oral vasodilators as intravenous vasodilators are to positive inotropes [41]. Intravenous nitroprusside, a direct
weaned nitrovasodilator, rapidly lowers filling pressures and improves
Adjust oral diuretics to keep optimal volume status cardiac output, which in turn, improves response to diuretic
therapy. Hemodynamically monitored nitroprusside infusions
CI, cardiac index; CVP, central venous pressure; PAP, pulmonary rarely cause systematic hypotension but may be complicated by
artery pressure; PCW, pulmonary capillary wedge pressure; SVR,
systemic vascular resistance. thiocyanate toxicity, particularly when high doses are required
Adapted from Stevenson LW: Tailored therapy to hemodynamic goals for prolonged periods of time in patients with preexisting hep-
for advanced heart failure. Eur J Heart Fail 1:251257, 1999 atic or renal dysfunction. Intravenous nitroglycerin also pro-
(Table 2, page 254), used with permission. duces arterial and venous dilatation but is less effective than
nitroprusside. Nesiritide, a human recombinant form of en-
dogenous BNP, rapidly improves symptoms. It has largely
been used for patients demonstrating the warm and wet
goals which generally include a pulmonary capillary wedge hemodynamic profile rather than those with more advanced
pressure below 15 mm Hg and a cardiac index above 2.2 L cool and wet profiles. A small study suggested that short-
per minute per m2 . This intravenous program is maintained term in-hospital nesiritide administration resulted in fewer re-
for 24 to 48 hours to effect desired diuresis and improve end- hospitalizations for heart failure and lower 6-month mortality
organ perfusion. Following this stage, oral vasodilators are up- following discharge compared with dobutamine [42]. How-
titrated as intravenous agents are weaned. Further adjustment ever, the safety of nesiritide has been questioned and the hope
in diuretic dose and ambulation should be completed during that this agent would attenuate renal dysfunction during heart
the final 24 to 48 hours of hospitalization. This tailored ap- failure treatment has not been realized [43]. Two retrospective
proach produces sustained improvement in filling pressures, post hoc analyses have suggested short-term nesiritide treat-
forward cardiac output, decreased mitral regurgitation, and de- ment may be associated with worsening renal function and
creased neurohormonal activation [23]. Oral vasodilator ther- may increase short-term mortality risk. Further, it has not been
apy and beta-blockers should be withheld during treatment studied extensively in patients with hypotension or hypoper-
with intravenous vasoactive agents. fusion. The ongoing ASCEND-HF trial of 4,500 patients will
Considerable controversy continues to exist regarding the address the safety and efficacy of short-term nesiritide therapy
relative roles of intravenous vasodilator drugs (i.e., nitro- in acute decompensated heart failure. Table 33.6 summarizes
glycerin, nitroprusside, or nesiritide) versus positive inotropic vasaactive agents used to manage of acute decompensated heart
agents (dobutamine, dopamine, or milrinone) in this popula- failure.
tion. Previously, inotropic infusions have been used for pa-
tients with moderate heart failure to promote brisk diuresis.
These agents, however, are associated with an increased risk of
Biomarker-Guided Therapy
ischemic events and tachyarrhythmias [40]. A second major The use of serial BNP or NT-pro-BNP to guide therapy remains
limitation of short-term inotropic support is the additional controversial. Small, controlled trials in ambulatory patients

TA B L E 3 3 . 6
INTRAVENOUS VASOACTIVE AGENTS FOR DECOMPENSATED HEART FAILURE

Drug Initial dose Maximal dose

Vasodilator
Nitroprusside 0.20 g/kg/min 10 g/kg/min
Nitroglycerin 10 g/kg/min 1,000 g/kg/min
Nesiritide Loading dose: 2 g/kg/min 0.030 g/kg/min
Maintenance dose: 0.01 g/kg/min
Positive inotropic agents
Dobutamine 2.5 g/kg/min 20 g/kg/min
Milrinone Loading dose: 50 g/kg 0.75 g/kg/min
Maintenance dose: 0.375 g/kg/min
Dopamine 2.5 g/kg/min 20 g/kg/min
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Chapter 33: Management of Advanced Heart Failure 325

with chronic heart failure demonstrated fewer heart failure The potential adverse effects of atrial fibrillation include loss
rehospitalizations using BNP to adjust pharmacologic therapy. of atrioventricular synchrony, rapid or inappropriately slow
However, this approach recently failed to improve survival free ventricular response rates, variable diastolic filling times, and
of repeat hospitalizations or quality of life in a large cohort of thromboembolic complications. Atrial fibrillation has been as-
patients [44]. A reasonable approach for inpatients with acute sociated with increased mortality and more frequent hospital-
decompensated heart failure should include the measurement izations in some, but not all, series [48]. Patients with a known
of BNP or NT-pro-BNP on admission and prior to discharge history of chronic atrial fibrillation should have adequate heart
when the patient is euvolemic, both for prognostic purposes as rate control and anticoagulation whenever feasible (see later).
well as to aid in tailoring postdischarge treatment [45]. Daily Uncontrolled, sustained, rapid (>120 beats per minute) atrial
biomarker measurement does not add significant prognostic fibrillation can result in a reversible dilated cardiomyopathy or,
value. A fall of 30% or greater in BNP or NT-pro-BNP iden- more typically, can worsen preexisting left ventricular systolic
tifies patients at low risk at discharge. Conversely, a rise in ei- dysfunction. A heart rate below 100 beats per minute during
ther biomarker suggests worsening disease or inadequate ther- modest ambulation is a reasonable goal. Beta-adrenergic block-
apy and should prompt a review of the patients heart failure ers and digoxin remain first-line rate-controlled treatment op-
regimen. tions [4]. Calcium channel blockers (e.g., diltiazem and vera-
pamil) should be avoided with advanced heart failure due to
their negative inotropic effects. Amiodarone is a highly effec-
tive drug for rate control and is frequently useful for controlling
PERIOPERATIVE MANAGEMENT persistent atrial arrhythmias in ICU patients [49].
OF ADVANCED HEART Atrial fibrillation commonly occurs during hospitalization
FAILURE PATIENTS due to enhanced sympathetic stimulation. In all patients, thy-
roid function should be assessed to exclude hyperthyroidism as
Nonemergent surgical procedures should be delayed until heart a contributor. For stable heart failure patients with atrial fib-
failure status has been optimized. Volume overload should rillation initial therapy should focus on adequate rate control
be corrected and adequate oxygenation insured. Maintenance (HR <100 per minute) using digoxin or beta-blockers, with
pharmacologic therapy including vasodilators, beta-blockers, pharmacologic or electrical cardioversion reserved for those
and digitalis should be continued. A trough digoxin level patients who in whom symptoms are refractory or those who
should be checked and maintained below 1 ng per dL to mini- are intolerant of conservative medical management. Patients
mize potential toxicity. Spironolactone should be withheld until who experience active angina pectoris or hemodynamic in-
stable hemodynamics and renal function have been achieved. stability during new onset atrial fibrillation should undergo
Patients with refractory symptoms or deteriorating end-organ urgent synchronized cardioversion with initiation of an atrial-
function should have a pulmonary catheter inserted to opti- stabilizing agent to prevent recurrence. For heart failure pa-
mize their hemodynamics. Current evidence does not support tients in whom restoration or maintenance of sinus rhythm is
the routine use of a pulmonary artery catheter for periopera- desirable, amiodarone, dofetilide, and sotalol remain the most
tive monitoring [11]. A single large-scale randomized clinical useful antiarrhythmic drugs [49]. In compensated heart failure,
trial of pulmonary artery catheterization in high-risk surgical amiodarone is well tolerated from a hemodynamic standpoint.
patients demonstrated no improvement in survival [46]. How- For patients with advanced heart failure symptoms or recent
ever, only 16% of patients enrolled in this trial had heart fail- decompensation, the loading dose of amiodarone should be
ure. Ejection fraction alone is insufficient to recommend the kept below 1,000 mg per day to prevent exacerbation of heart
use of continuous hemodynamic monitoring. Many patients failure. Dronedarone, a new noniodinated derivative of amio-
with markedly impaired ventricular function (LVEF <20%) darone, has been shown to be effective for maintenance of si-
may be well compensated on optimized pharmacologic therapy nus rhythm and rate-control in rapid atrial fibrillation [50].
and undergo surgery without invasive monitoring. Conversely, However, increased mortality due to worsening heart failure
some patients with only moderate impairment in LVEF may has been reported in one recent controlled trial [1,49]. Until
benefit from pulmonary artery monitoring when hemodynamic additional data are available, this agent should not be used
instability is anticipated. Practice guidelines for intraoperative for patients with severe systolic dysfunction or hemodynamic
hemodynamic monitoring published by the American Society instability.
of Anesthesiologists consider the severity of the patients un- Dofetilide is a class III antiarrhythmic drug that blocks the
derlying cardiovascular disease, the type of surgical procedure, repolarizing potassium current. It is highly effective in restoring
and the likelihood of major hemodynamic lability [47]. The ex- sinus rhythm but is associated with torsades de pointes in up to
tent of anticipated intraoperative and perioperative fluid shifts 3% of patients [49]. Continuous ECG monitoring for the first
is another key factor. Current ACC/AHA guidelines recom- 48 hours after initiation in the hospitalized patient is essential.
mend intraoperative pulmonary artery monitoring as a Class Sotalol, an additional class III antiarrhythmic drug, may occa-
2B indication as indicated for patients at risk for major hemo- sionally be substituted for other beta-blockers in heart failure
dynamic disturbances that are easily detected by pulmonary patients, but carries with it a similar risk of torsades, and is
artery catheter who are scheduled to undergo a procedure that generally less effective than amiodarone.
is likely to cause these hemodynamic changes [11]. Asymptomatic nonsustained ventricular tachycardia
(NSVT) occurs in over 50% of patients with NYHA class
III/IV heart failure. Pharmacologic suppression of NSVT does
not lower the risk of sudden death. Asymptomatic ventricular
MANAGEMENT OF ectopy should be viewed as a marker of disease severity
ARRHYTHMIAS rather than a specific marker for sudden cardiac death risk
[51]. Heart failure patients often develop frequent ventricular
Atrial and ventricular arrhythmias are nearly ubiquitous in ad- premature beats or short runs of NSVT during their ICU
vanced heart failure patients and often contribute to clinical stay. Precipitating causes such as electrolyte disturbances
decompensation. Atrial fibrillation and flutter are the most (hypokalemia or hypomagnesemia), enhanced sympathetic
commonly encountered supraventricular arrhythmias. The tone, a decrease in beta-blocker dose, or withholding of prior
likelihood of atrial fibrillation increases with heart failure sever- antiarrhythmic therapy should be considered. The majority of
ity and approaches 40% for NYHA class III and IV patients. patients have no symptoms and do not require pharmacologic
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326 Section III: Cardiovascular Problems and Coronary Care

TA B L E 3 3 . 7
RESULTS OF RANDOMIZED TRIALS OF PHARMACOLOGIC TREATMENT AND ULTRAFILTRATION IN ACUTE
DECOMPENSATED HEART FAILURE

No. of
Intervention Trial Year Study patients Findings Reference

Hydralazine- A-HeFT 2004 RCT 1,050 43% reduction in all-cause 25


Nitrates mortality in blacks
Carvedilol COPERNICUS 2002 RCT 2,289 31% reduction in death or 32
HF hospitalizations in
NYHA class III/IV patients
Milrinone OPTIME-CHF 2002 RCT 951 No reduction in 40
hospitalizations for cardiac
causes within 60 days of
treatment with milrinone
for ADHF
Ultrafiltration UNLOAD 2007 RCT 200 UF resulted in greater weight 19
loss and fewer
rehospitalizations for heart
failure
Pulmonary artery ESCAPE 2005 RCT 433 PAC for tailoring of therapy 39
catheter (PAC) did not lower mortality or
placement rehospitalizations
Nesiritide vs. 2002 Open label 261 Nesiritide resulted in fewer 42
dobutamine randomized readmissions and lower
6-month mortality than
dobutamine
Nesiritide NAPA 2007 RCT 279 Nesiritide improved renal
function after CABG

ADHF, acute decompensated heart failure; A-HeFT, African American Heart Failure Trial; CABG, coronary artery bypass grafting; COPERNICUS,
Carvedilol Prospective Randomized Cumulative Survival Study; ESCAPE, Evaluation Study of Congestive Heart Failure and Pulmonary Artery
Catheterization Effectiveness; NAPA, nesiritide-administered perianesthesia in patients undergoing cardiac surgery; RCT, randomized controlled trial;
OPTIME-CHF, Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbation of Chronic Heart Failure.

suppression. Frequent runs of ventricular tachycardia or sufficient to warrant systemic anticoagulation. Warfarin should
sustained monomorphic VT require antiarrhythmic treatment. be continued with an INR goal of 2.0 to 3.0 if invasive proce-
Amiodarone (intravenous 0.50 to 1.0 mg/min) or lidocaine dures are not planned. If surgery or central venous catheter
(0.5 to 2 mg per min) is generally most effective for acute placement is required, warfarin can be reversed with vita-
management. Beta-blockers, sotalol, and amiodarone are min K or fresh frozen plasma and transiently substituted with
effective long-term oral treatment options. intravenous heparin or subcutaneous low-molecular weight
A growing percentage of advanced heart failure patients heparin as feasible. For those patients who require anticoagu-
have implantable cardioverter defibrillators (ICDs) to treat lation but are unable to receive heparin (e.g., due to heparin-
symptomatic ventricular tachyarrhythmias or for primary pre- induced thrombocytopenia), alternative anticoagulants includ-
vention of sudden cardiac death. The ICD should be interro- ing the direct thrombin inhibitors argatroban and hirudin, or
gated for any recent atrial or ventricular arrhythmias prior to the pentasaccharide fondaparinux can be considered.
admission and the device temporarily inactivated prior to sur-
gical procedures that involve electrocautery. It should be re-
activated and its function checked by an electrophysiologist in
the early perioperative period. CONCLUSION
The patient with advanced heart failure requires special con-
Anticoagulation siderations. Meticulous attention to volume status and mainte-
nance of appropriate vasodilator therapy and beta-adrenergic
Systemic anticoagulation is often a part of a heart failure pa- blockade form the cornerstones of acute management (Table
tients outpatient management. Studies have suggested that the 33.7). Negative inotropic drugs and agents that might fur-
risk of thromboembolic complications is lower than previ- ther impair renal function should be avoided. Patients with
ously expected, averaging 1.5 to 3 episodes per 100 patient refractory symptoms or recent decompensation may require
years when normal sinus rhythm is present. Current indications hemodynamic monitoring via a pulmonary artery catheter and
for systemic anticoagulation include paroxysmal or chronic initiation of short-term vasoactive therapy including nitro-
atrial fibrillation, a history of thromboembolism, or echocar- prusside, nitroglycerin, nesiritide, milrinone, or dobutamine.
diographically documented left ventricular thrombus. Relative Maintenance of sinus rhythm and suppression of recurrent
indications include a markedly dilated left ventricle (>75 mm) ventricular tachyarrhythmias is mandatory. With careful man-
with severe systolic dysfunction and spontaneous echocardio- agement, hospital morbidity and mortality can be minimized
graphic contrast (smoke) indicating sluggish intracavitary despite the presence of severe ventricular systolic or diastolic
blood flow. The presence of a low ejection fraction alone is in- dysfunction.
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Chapter 33: Management of Advanced Heart Failure 327

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P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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328 Section III: Cardiovascular Problems and Coronary Care

CHAPTER 34 VALVULAR HEART DISEASE


GARRICK C. STEWART AND PATRICK T. OGARA

The incidence of valvular heart disease continues to rise due Older age, male sex, smoking, diabetes mellitus, hypertension,
to the increasing longevity of the population and remains a chronic kidney disease, and hypercholesterolemia are risk fac-
source of significant morbidity and mortality [1]. More than tors for calcific AS. Despite the compelling connection between
5 million Americans are living with valvular heart disease and atherosclerosis and calcific valve degeneration, high-dose lipid
nearly 100,000 undergo valve surgery each year [2]. Patients lowering therapy has thus far not been shown to retard the
with native or prosthetic valve disease constitute a signifi- progression of AS in randomized trials [7,8].
cant proportion of intensive care unit (ICU) admissions. Many Congenitally bicuspid aortic valves are present in 1% to
patients come to medical attention during an acute illness that 2% of the population, with a 4 to 1 male predominance, and
triggers an abrupt change in cardiovascular physiology. While seldom result in serious narrowing of the aortic orifice dur-
stabilization with medical management is possible for most ing childhood [9]. Abnormal valve architecture makes the two
patients with mild or moderate disease, surgery may be ur- cusps susceptible to hemodynamic stresses, ultimately leading
gently required if severe disease is present. Prompt diagnosis to thickening, calcification, and fusion of leaflets, and narrow-
often requires a high index of suspicion [3]. Timely cardiac ing of the orifice. AS develops earlier in bicuspid valves, usu-
imaging with transthoracic echocardiography (TTE) can define ally in the fifth or sixth decades, compared with trileaflet aortic
valve anatomy and lesion severity. Transesophageal echocar- valves, which usually do not exhibit calcific AS until the sixth or
diography (TEE) may be required in select circumstances for seventh decade of life [10]. Bicuspid aortic valves are also asso-
better visualization and characterization. The need for an inva- ciated with aortic regurgitation (AR) and aortic root/ascending
sive hemodynamic assessment may follow. Early collaboration aortic dilatation and coarctation (Fig. 34.2). Up to 25% to
among intensivists, cardiologists, and cardiac surgeons is criti- 40% of patients with bicuspid aortic valve will have an as-
cal for optimizing patient outcome. This chapter will highlight cending aortic aneurysm unrelated to the severity of the valve
an integrated approach to the diagnosis and treatment of the lesion. Patients with bicuspid aortic valves are susceptible to
native and prosthetic valve diseases most commonly encoun- aortic dissection [11]. Medial degeneration similar to that seen
tered in an ICU setting. in Marfan syndrome is responsible for aneurysm development
in patients with a bicuspid aortic valve [12].
Rheumatic disease may affect the aortic leaflets leading to
AORTIC STENOSIS commissural fusion, fibrosis, and calcification, with narrowing
of the valve orifice. Rheumatic AS is almost always accom-
Aortic stenosis (AS) is a progressive disease for which there is panied by involvement of the mitral valve and concomitant
no medical treatment. The ICU management of patients with AR. Radiation-induced AS as a sequela of cancer radiotherapy
AS may be quite challenging, particularly in the setting of con- often occurs in conjunction with proximal coronary artery dis-
comitant medical illness. Characterizing the severity of steno- ease (CAD). Rare causes of valvular AS include Pagets disease
sis is critical for determining the timing of surgical intervention of bone, rheumatoid arthritis, and ochronosis. By the time AS
and requires a careful history, physical examination, and initial becomes severe, superimposed calcification may make it diffi-
imaging with TTE. cult to determine underlying valve architecture and the precise
etiology.
In addition to valvular AS, other causes of left ventricular
Etiology (LV) outflow obstruction include hypertrophic obstructive car-
diomyopathy (HOCM), a congenitally unicuspid aortic valve,
AS accounts for one-quarter of all chronic valvular heart dis- discrete congenital subvalvular AS resulting from a fibromus-
ease, with approximately 80% of symptomatic cases occurring cular membrane, and supravalvular AS. The various causes of
in adult males (Fig. 34.1). Common etiologies of valvular AS LV outflow obstruction can be differentiated by careful physi-
include age-related calcific degeneration, stenosis of a congen- cal examination and TTE.
itally bicuspid valve, and rheumatic heart disease. Age-related,
degenerative calcific AS is the most common cause of AS among
adults in the United States. More than 30% of adults older Pathophysiology
than 65 years exhibit aortic valve sclerosis, whereas only 2%
have more significant valvular stenosis. The valve cusps are fo- Obstruction to LV outflow produces a pressure gradient be-
cally thickened or calcified in aortic sclerosis, with production tween the LV and the aorta (Fig. 34.3). The ventricle responds
of a systolic ejection murmur, but without significant outflow to this pressure overload with concentric hypertrophy, which
obstruction (peak jet velocity of <2.5 m per second). Recent is initially adaptive because it reduces wall stress and preserves
studies suggest calcific AS is the end result of an active disease ejection performance. The law of Laplace states that wall stress
process rather than the inevitable consequence of aging [4]. is directly proportional to the product of LV pressure and ra-
There may also be a genetic predisposition to calcific degen- dius and inversely proportional to LV wall thickness. Compen-
eration of trileaflet valves [5]. The histologic appearance of a satory hypertrophy may accommodate a large pressure gradi-
sclerotic valve is similar to atherosclerosis, with inflammation, ent for years before it becomes maladaptive and LV function
calcification, and thickening. Both calcific AS and aortic sclero- declines, with chamber dilatation and reduced cardiac output
sis appear to be a marker for coronary heart disease events [6]. [13]. In the setting of AS with preserved ejection fraction (EF),
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Chapter 34: Valvular Heart Disease 329

A B

FIGURE 34.1. Transthoracic echocardiography of severe valvular aortic stenosis. A: Transthoracic


echocardiogram parasternal long axis view of the aortic valve during systole. Aortic valve leaflets are
thickened with severely restricted motion consistent with severe aortic stenosis. B: Transaortic continuous
wave Doppler jet from the apical five-chamber view. Peak transaortic velocity is 4.68 m/sec, producing an
estimated peak transaortic gradient of 87 mm Hg.

cardiac output may be normal at rest but fail to rise appro- toms because of the reliance on atrial systole to fill the stiff,
priately with exercise. Coronary flow reserve may be reduced hypertrophied LV.
because of the increased oxygen demand of the hypertrophied No single parameter of valve structure or function is suffi-
LV and increased transmural pressure gradient, and the longer cient to define the severity of AS. Integration of the clinical his-
distance blood must travel to reach the subendocardial layer. tory, physical examination, and TTE is required to place the le-
Taken together, these factors can contribute to subendocardial sion in context [15]. The physical examination of AS in the ICU
ischemia even in the absence of epicardial CAD [14]. The loss may be particularly challenging, contributing to the greater
of appropriately timed atrial contraction, such as occurs with importance of timely TTE. Echocardiographic criteria for se-
atrial fibrillation (AF), may cause rapid progression of symp- vere AS in patients with normal underlying LV function include

A B

FIGURE 34.2. Bicuspid aortic valve and aortic root aneurysm. A: Transthoracic echocardiogram with
parasternal short axis view at the level of the aortic valve reveals a bicuspid aortic valve with fusion of the
left and noncoronary cusps. B: A 5.1-cm ascending aortic aneurysm in a 37-year-old man with bicuspid
aortic valve disease and only moderate aortic stenosis (valve area, 1.2 cm2 ). Patients with bicuspid disease
frequently develop aneurysms of the ascending aorta independent of the severity of hemodynamic valvular
impairment and are at risk for aortic dissection. Resection is indicated for maximal aneurysm size larger
than 5.0 cm, an increase in aneurysm size of more than 0.5 cm/y, or at the time of aortic valve replacement
if the aneurysm size exceeds 4.5 cm. [From Libby P (ed): Essential Atlas of Cardiovascular Disease. New
York, NY, Springer, 2009, p 216, Figure 96, with permission.]
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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330 Section III: Cardiovascular Problems and Coronary Care

TA B L E 3 4 . 1
Aortic stenosis
SEVERITY OF AORTIC STENOSIS

LV outflow obstruction Severity of Valve area Mean gradient Jet velocity


stenosis (cm2 ) (mm Hg) (msec)

LV systolic LVET LV diastolic AO pressure Mild >1.5 <25 <3.0


pressure pressure Moderate 1.01.5 2540 3.04.0
Severe <1.0 >40 >4.0
LV mass

LV dysfunction vasodilatation in the presence of a fixed cardiac output or an


Myocardial Diastolic
inappropriate baroreceptor reflex. Severe AS is also rarely asso-
O2 consumption time ciated with acquired von Willebrands disease related to sheer-
ing of von Willebrand multimers passing through the stenotic
Myocardial
orifice [19]. As a result, gastrointestinal bleeding, epistaxis, or
O2 supply ecchymoses may be present in some patients.
Most patients with AS have gradually increasing LV ob-
struction over many years, producing a long latent phase. Dur-
Myocardial ing this clinically silent period, there is a very low risk of sudden
ischemia death (<1% per year) [20]. The rate of AS progression is vari-
able, with an average increase in mean gradient of 7 mm Hg
LV failure and reduction in valve area of 0.1 cm2 per year [21]. Symptoms
from valvular AS are rare until the valve orifice has narrowed
to approximately less than 1 cm2 . The onset of symptoms is
FIGURE 34.3. Pathophysiology of aortic stenosis. Left ventricular a critical turning point in the natural history of the disease,
(LV) outflow obstruction results in a gradual increase in LV systolic usually indicates severe AS, and heralds the need for surgical
pressure, an increase in LV ejection time (LVET), an increase in LV evaluation and treatment because of the markedly reduced sur-
diastolic pressure, and a decrease in mean aortic (Ao) pressure. In- vival [17] (Fig. 34.4). An abrupt change in the natural history of
creased LV systolic pressure results in compensatory LV hypertrophy
(LVH), which may lead to LV dysfunction and failure. Increased LV sys-
AS may occur with AF, endocarditis, or myocardial infarction
tolic pressure, LVH, and prolonged LVET increase myocardial oxygen (MI), each of which may trigger acute decompensation [22].
(O2 ) consumption. Increased LVET results in a decrease in LV dias-
tolic time (myocardial perfusion time). Increased LV diastolic pressure Physical Examination
and decreased Ao diastolic pressure decrease coronary perfusion pres-
sure, thereby decreasing myocardial supply. Increased myocardial O2 The hallmark of AS is a carotid arterial pulse that rises slowly
consumption and decreased myocardial O2 supply produce myocar- to a delayed peak, known as pulsus parvus et tardus. In the el-
dial ischemia, which further compromises LV function. [Adapted from derly, stiffened carotid arteries may mask this finding. Similarly,
Bonow R, Braunwald E: Valvular heart disease, in Zipes D, et al. (eds): patients with AS and concomitant AR may have preservation
Braunwalds Heart Disease. Philadelphia, Elsevier, 2005, p 1585, with of the arterial upstroke due to an elevated stroke volume. The
permission.] LV apical impulse may be displaced laterally with a sustained
contour due to LV hypertrophy (LVH) and prolonged systolic
ejection.
calcified leaflets with reduced excursion, maximal transaortic The murmur of AS is a systolic ejection murmur commenc-
jet velocity of more than 4 m per second, mean transaortic ing shortly after S1, rising in intensity with a peak in mid
gradient of more than 40 mm Hg, or an effective aortic valve ejection, then ending just before aortic valve closure. It is
orifice of less than 1 cm2 (Table 34.1). When there is underly-
ing LV systolic dysfunction, severe AS may be present despite
low transaortic velocity and mean gradient. Such patients are
Onset
at particularly high risk for complications and require further Severe Symptoms
evaluation to determine if true valvular AS is present or whether 100

the reduced valve area relates to an underlying cardiomyopathy Latent Period Angina
(Increasing Obstruction,
(pseudo-severe AS) [16]. 80
Myocardial Overload) Syncope
Failure
60
0 2 4 6
Clinical Presentation Av SURVIVAL (Yrs)
40
History
The cardinal symptoms of AS are dyspnea, angina, and syncope 20 Average Death
[17]. Exertional dyspnea is typically the first reported symptom Age ( )

and reflects an elevation in LV end-diastolic pressure transmit-


ted to the pulmonary venous circulation. Some patients, partic- 0 40 50 60 70 80
ularly the elderly, may report generalized fatigue and weakness
Age (Years)
rather than dyspnea. Angina occurs in two thirds of patients
with AS and is similar to that reported by patients with flow- FIGURE 34.4. The onset of symptoms in patients with aortic stenosis
limiting coronary atherosclerosis [18]. Syncope is effort related initiates a rapid rise in the risk of mortality. Patients with angina have a
and due to cerebral hypoperfusion from a decrease in mean better prognosis than those with syncope. [From Ross J Jr, Braunwald
arterial pressure produced by the combination of peripheral E: Aortic stenosis. Circulation 38(1S5):6167, 1968, with permission.]
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Chapter 34: Valvular Heart Disease 331

characteristically low-pitched, harsh, or rasping in character Cardiac Catheterization


and best heard at the base of the heart in the second right
Noninvasive assessment with TTE is now standard, but
intercostal space. The AS murmur radiates along the carotid
catheterization may be helpful if there is a discrepancy be-
arteries, though may sometimes be transmitted downward to
tween the clinical and echocardiographic findings. Calculation
the apex where it may be confused with the murmur of mitral
of aortic valve area by invasive hemodynamic assessment re-
regurgitation (MR) (Gallavardin effect). The murmur of AS is
quires accurate assessment of the transvalvular flow and mean
diminished with Valsalva maneuver and standing, in contrast to
transvalvular pressure gradient to calculate effective orifice
the murmur of hypertrophic cardiomyopathy which gets louder
area using the Gorlin formula [23]. Concerns have been raised
with these maneuvers. Often S2 becomes paradoxically split in
about the risk of cerebral embolization during attempts to cross
severe AS because of prolonged LV ejection. An S4 is audible
the aortic valve and directly measure the transaortic gradient.
at the apex and reflects LVH with an elevated LV end-diastolic
Angiography is indicated to detect CAD in patients older than
pressure. An S3 gallop generally occurs late in the course of
45 years who are being considered for operative treatment of
AS when LV dilatation is present. Murmur intensity does not
severe AS [24]. Coronary CT angiography is likely to be per-
necessarily correspond to AS severity. The best predictors of
formed more often for this indication in patients with a low
AS severity on physical examination are a late peaking systolic
pretest likelihood of CAD.
murmur, a single S2 (absent aortic valve closure sound), and
pulsus parvus et tardus. In patients with heart failure and a low
cardiac output, the findings related to AS are less impressive. Special Case: Low-Output/Low-Gradient
Aortic Stenosis
The evaluation and management of patients with AS and a de-
Investigations pressed EF can be vexing. Patients with anatomically severe AS
and reduced EF (<40%) often have a relatively low-pressure
Electrocardiography gradient (<30 mm Hg) due to a weakened ventricle and af-
terload mismatch. The true severity of AS can be difficult to
Most patients with severe AS will have evidence of LVH on determine when the cardiac output and transaortic gradient
electrocardiogram (ECG). Left atrial (LA) enlargement is com- are low. If the ventricle itself is diseased and unable to generate
mon. Nonspecific ST and T wave abnormalities may be seen or sufficient systolic force to open the leaflets adequately, a re-
evidence of LV strain may be apparent. Rarely, atrioventricular duced aortic valve area may be present at rest, overestimating
conduction defects may develop due to extension of perivalvu- AS severity. This condition is known as pseudo-severe AS [25].
lar calcium into the adjacent conduction system. This finding In such cases, LV dysfunction is the predominant pathology
is more common after aortic valve replacement (AVR). There and may be caused by prior MI or a primary cardiomyopathy.
is poor correlation between ECG findings and AS severity. Patients either with true severe AS with reduced EF or pseudo-
severe AS have a low-flow state with low transaortic gradients
Chest Radiography contributing to calculated aortic valve areas less than 1 cm2 .
Pseudo-severe AS patients must be distinguished from those
The chest radiograph may be normal in severe AS. There may be
with true severe AS and poor LV function, since patients with
poststenotic dilation of the ascending aorta or a widened me-
true severe AS and contractile reserve will usually benefit from
diastinum if aortic aneurysmal dilatation is present in patients
valve surgery, whereas patients with pseudo-severe AS are not
with a bicuspid aortic valve. LV chamber size is usually nor-
operative candidates [2628].
mal, though aortic valve calcification may be seen, especially
Dobutamine stress echocardiography has a well-defined di-
on the lateral film. Valvular calcium deposits can be visualized
agnostic role in this setting [29] (Fig. 34.5). The inotropic ef-
using fluoroscopy during cardiac catheterization, chest com-
fects of low-dose dobutamine will increase transvalvular flow
puted tomography (CT), or TTE. A normal radiograph does
in patients with a contractile reserve [30]. Contractile reserve is
not exclude severe AS. In the later stages of AS, the LV dilates
defined as an increase in stroke volume with inotropic infusion
leading to a widened cardiac silhouette, often accompanied by
of more than 20%. Dobutamine infusion, particularly at doses
pulmonary congestion.
20 g per kg per minute, is generally well tolerated but should
only be performed in experienced centers with a cardiologist in
Echocardiography attendance. In patients with true severe AS and LV dysfunction,
TTE with Doppler is indicated for assessing the severity of dobutamine will increase cardiac output and mean transvalvu-
AS. TTE visualizes aortic valve structure, including the num- lar gradient, but the calculated aortic valve area will remain
ber of cusps, degree of calcification, leaflet excursion, annu- low (<1 cm2 ). Patients with pseudo-severe AS will have an in-
lar size, and supravalvular anatomy. Eccentric valve cusps are crease in aortic valve area into a range no longer considered
characteristic of congenitally bicuspid aortic valves, often ac- severe (>1.2 cm2 ) with little change in transvalvular gradient.
companied by aneurysmal enlargement of the root or ascend- Some patients will not show contractile reserve to dobutamine,
ing aorta. TTE is also useful for identifying coexisting valvular signaling a poor prognosis [31]. Surgery is indicated in true se-
disease, differentiating valvular AS from other forms of LV vere AS with contractile reserve after dobutamine challenge,
outflow tract obstruction, assessing pulmonary artery systolic and generally contraindicated for patients with pseudo-severe
pressure, and evaluating underlying biventricular function. The AS or those without contractile reserve [32]. Patients with
peak transvalvular jet velocity on continuous wave Doppler is low-gradient AS undergoing AVR have a significantly higher
critical for assessing AS severity. Peak and mean transvalvular perioperative and long-term mortality if multivessel CAD is
gradients are derived from the jet velocity using the modified present [27,33].
Bernoulli equation and the aortic valve area is estimated from
the continuity equation. The dimensionless index, which is the
ratio of LV outflow tract velocity to peak aortic velocity, can Intensive Care Unit Management
also be used to estimate AS severity when measurement of LV
outflow tract diameter is difficult due to extensive calcification. Surgery with AVR is the preferred treatment strategy for pa-
A dimensionless index less than 0.25 is consistent with severe tients with symptomatic severe AS and for asymptomatic pa-
AS [15]. tients with severe AS who have a reduced EF (<50%). In
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332 Section III: Cardiovascular Problems and Coronary Care

FIGURE 34.5. Decision making in low-flow, low-gradient aortic stenosis (AS). Dobutamine stress
echocardiography aids decision making in low-flow AS. Contractile reserve is defined as an increase in
stroke volume of >20%. When contractile reserve is elicited, patients with true severe AS have an increase
in transvalvular gradient (P) with a persistently low calculated valve area (AVA). One can also determine
the projected AVA at a standardized normal flow rate (AVAproj ), with an AVAproj 1 cm2 consistent with
true severe AS. Management decisions are more challenging if contractile reserve is absent. AVR, aortic
valve replacement; CABG, coronary artery bypass grafting; LV, left ventricle. [From Picano E, Pibarot P,
et al: The emerging role of exercise testing and stress echocardiography in valvular heart disease. J Am
Coll Cardiol 54:22512260, 2009, with permission.]

contrast, surgery may be postponed in patients with severe, Medical Management


asymptomatic AS and normal LV function, as these patients
Medical interventions in severe AS are largely supportive until
may do well for years [34]. AVR is also indicated for patients
surgery is feasible. In patients with severe AS with heart fail-
with moderate AS who require other cardiac surgery, such as
ure or cardiogenic shock, management should be guided by
coronary artery bypass grafting (CABG) or aortic aneurysm
invasive hemodynamic monitoring with a pulmonary artery
repair. Patients with severe AS and cardiogenic shock may
catheter. Gentle diuresis may relieve pulmonary congestion,
be considered for percutaneous aortic balloon valvuloplasty
but patients with severe AS have a preload-dependent state,
(PABV) as a bridge to AVR. Transcatheter aortic valve implan-
so overdiuresis can cause a severe drop in blood pressure. For
tation (TAVI) has been performed in more than 5,000 patients
patients in cardiogenic shock, arterial pressure should be sup-
worldwide and promises to be a viable treatment alternative
ported with inotropes and/or vasopressors until valve surgery
for patients with severe AS who are considered too high risk
can be performed. Vasodilators are generally contraindicated,
for conventional surgery.
except in select patients with depressed EF [35]. In these
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Chapter 34: Valvular Heart Disease 333

select patients with EF less than 35%, severe AS and cardio- but accurate diagnosis may be a challenge because examination
genic shock accompanied by high systemic vascular resistance, findings may be subtle and the clinical presentation nonspe-
sodium nitroprusside infusion has been shown to modestly im- cific [52]. Patients with acute AR appear gravely ill and have
prove hemodynamics and can serve as a bridge to the operating tachycardia, significant dyspnea, and often hypotension. The
room [36]. presentation of acute AR may even be mistaken for other acute
conditions like sepsis, pneumonia, or nonvalvular heart failure.
In marked contrast, chronic severe AR may be asymptomatic
Surgical Treatment or minimally symptomatic and is rarely encountered in the ICU
AVR is the preferred treatment for severe symptomatic AS setting. In cases of acute valvular regurgitation, a high index
[32,37]. Choice of valve prosthesis depends on patient age, of suspicion is required, along with timely TTE, and prompt
anticipated lifespan, and preference for and tolerance of anti- surgical consultation.
coagulation [38]. The perioperative mortality for isolated AVR
ranges from less than 1% in healthy, younger patients with
normal LV systolic function to 10% or more in elderly patients Etiology
with coexisting CAD and reduced EF. Age alone is not a con-
traindication to AVR. Other factors associated with reduced Most cases of acute severe AR are caused by infective endo-
survival after AVR include chronic kidney disease, obstructive carditis (IE), but other causes include aortic dissection and
lung disease, reoperation, emergency operation, and age older blunt chest trauma. Staphylococcus has emerged as the most
than 65 years. The overall 10-year survival for patients with important causative organism of native valve endocarditis
AVR is approximately 60%. Surgical risk for valve replacement [53,54]. Patients with antecedent aortic valve disease or a con-
can be estimated using one of several online calculators (Soci- genital bicuspid valve are at increased risk for IE, though organ-
ety for Thoracic Surgeons, EuroSCORE, or others) [3941]. isms like Staphylococcus aureus can infect a normal trileaflet
valve. IE is a particular problem among injection drug users,
patients with indwelling catheters, and those on hemodialysis.
Acute severe AR from IE is the consequence of tissue destruc-
Percutaneous Aortic Balloon Valvuloplasty and tion, leaflet perforation, or bulky vegetations impairing leaflet
Percutaneous Valve Replacement coaptation [55].
PABV is often used instead of an operation in children and AR is present in up to 65% of patients with Stanford Type
young adults with congenital, noncalcific AS. During the pro- A aortic dissection [56]. Ascending aortic dissection may be
cedure in adults, a balloon is placed across the stenotic aortic seen in Marfan syndrome, bicuspid aortic valve, or following
valve and inflated to high pressure to fracture adherent calcium CABG or AVR surgery. Retrograde extension of the dissection
and increase effective orifice area [42]. A technically success- flap into the annulus may cause prolapse or eversion of the
ful procedure can reduce the transaortic valve gradient to a aortic valve leaflets. Type A aortic dissection with AR is a sur-
mild degree but rarely increase valve area to more than 1 cm2 . gical emergency requiring prompt diagnosis and intervention
Valvuloplasty is not widely used in adults with severe calcific [57]. Aneurysmal enlargement of the aortic root without dis-
AS because of high restenosis rates, frequent embolic compli- section may also lead to AR. Although AR is usually chronic
cations (particularly stroke), and the development of AR [43]. when produced by aortic root dilatation, an acute-on-chronic
In adults with acutely decompensated AS, PABV is particularly decompensation may occur if there is superimposed dissection
high risk and has no proven long-term benefits [44]. Given these or abrupt aneurysm enlargement [58]. Important causes of aor-
risks, PABV is seldom used even in a palliative setting. In rare tic root pathology producing AR include connective tissue dis-
cases, it may be used as a bridge to AVR in patients with severe orders (Marfan syndrome and Ehlers-Danlos syndrome) and
LV dysfunction and shock who are too ill to tolerate surgery vasculitis (syphilis aortitis, giant cell arteritis, or Takayasus
without a period of metabolic recovery. PABV should not be arteritis). Aortic leaflets tears, perforation, or detachment pro-
considered as a substitute for AVR. ducing AR may also follow blunt chest trauma or occur as a
TAVI has generated considerable enthusiasm because it can complication of PABV for AS [59].
eliminate the incremental risks conferred by sternotomy, car-
diopulmonary bypass, and general anesthesia. TAVI can now
be achieved in select patients and is undergoing active clini- Pathophysiology
cal investigation [4548]. The procedure involve preparatory
PABV followed by deployment of a balloon or self-expanding Unlike in chronic AR, the LV in acute AR has not had time to
stented valve across the stenotic orifice. An antegrade, retro- develop compensatory eccentric hypertrophy in response to el-
grade or LV transapical approach may be used. The retrograde evated afterload and preload (Fig. 34.6). The nondilated, non-
approach is preferred but depends critically on whether rel- compliant left ventricle receives a significant diastolic volume
atively large diameter catheters can be successfully manipu- load from the regurgitant flow, resulting in an abrupt rise in
lated through the arterial system. Lower profile devices are LV end-diastolic pressure. This pressure may in turn be trans-
under active development. There are several potential com- mitted to the pulmonary bed resulting in pulmonary edema.
plications, though results with TAVI have been improving Since the LV cannot dilate acutely in response to the volume
steadily and are quite promising [49]. TAVI will likely to have load, forward stroke volume is decreased and tachycardia de-
a major impact on management of AS in elderly, high-risk velops to maintain cardiac output. Impaired forward stroke
patients [50,51]. volume leads to decreased systolic pressure and relatively nar-
row pulse pressure. Patients may present with signs of impend-
ing cardiogenic shock. LV diastolic pressure may equilibrate
with aortic pressure during the latter half of diastole (diastasis),
AORTIC REGURGITATION resulting in attenuation of the AR murmur in the acute setting.
The elevation in end-diastolic pressure and tachycardia can
Acute severe AR may occur in previously normal or only mildly increase myocardial oxygen demand and, when coupled with
diseased valves and often results in abrupt hemodynamic de- decreased diastolic coronary blood flow, can reduce myocar-
compensation and respiratory compromise requiring ICU ad- dial perfusion and result in coronary ischemia. Ischemia from
mission. Acute valvular regurgitation is a surgical emergency, AR can be compounded by impairment in coronary flow from
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334 Section III: Cardiovascular Problems and Coronary Care

Acute aortic Investigations


regurgitation
Electrocardiography
Sinus tachycardia is often present, though the ECG may be en-
Increased LV Decreased stroke tirely normal in acute severe AR. In contrast, LVH is a feature of
diastolic volume volume Equilibration of
LVEDP with aortic
chronic AR. Nonspecific ST-segment and T-wave abnormalities
diastolic pressure or signs of LV strain are common. In IE, if there is paravalvular
extension of the infection in the region of the atrioventricular
node, heart block of varying degree may be present. In the
setting of acute heart failure, supraventricular and ventricular
Increased LVEDP Tachycardia Decreased tachycardias may occur.
coronary perfusion
pressure and
myocardial
Chest Radiography
Increased oxygen delivery The cardiac silhouette may be normal unless AR is chronic or
myocardial oxygen
there was preexisting heart disease. Pulmonary edema is com-
consumption
mon and characterized by cephalization of interstitial markings
Myocardial and Kerley B lines. A widened mediastinum may signify aortic
ischemia dissection or thoracic aortic aneurysm.

LV dysfunction and Echocardiography


failure
Urgent TTE is mandated whenever acute AR is suspected.
Echocardiography can determine etiology and hemodynamic
FIGURE 34.6. Pathophysiology of acute aortic regurgitation. LV, left severity of AR while providing information on underlying LV
ventricle; LVEDP, left ventricular end diastolic pressure. [Adapted from function, aortic size, and coexisting valvular heart disease (Fig.
Bonow R, Braunwald E: Valvular heart disease, in Zipes D, et al. (eds): 34.7). Severe AR is characterized by a wide regurgitant jet (vena
Braunwalds Heart Disease. Philadelphia, Elsevier, 2005, with permis-
contracta >6 mm) and holodiastolic flow reversal in the de-
sion.]
scending thoracic aorta [60]. The rapid rise in LV diastolic
pressure with acute severe AR produces short pressure half
time (<250 milliseconds) and premature mitral valve closure
[61]. CT angiography has become the preferred imaging test
preexisting atherosclerosis or an aortic dissection flap. In acute to assess for acute dissection, but TEE may be indicated if the
severe AR, LV failure and cardiogenic shock develop if surgery study is nondiagnostic and can be crucial for surgical planning
is not promptly performed. [62,63].

Cardiac Catheterization
Clinical Presentation Establishing the hemodynamic severity of AR seldom requires
catheterization, which can delay surgery [64]. Younger patients
History without coronary risk factors may proceed directly to emer-
gency valve replacement without angiography. Patients with
Acute AR may present with little or no warning. Symptoms
Type A dissection should proceed directly to surgical repair.
of weakness, profound dyspnea, angina, and presyncope are
common. Antecedent valve disease, fever, and skin findings may
suggest IE. Severe, ripping chest or back pain with hypertension
may indicate aortic dissection. Signs of blunt chest trauma may Intensive Care Unit Management
be disarmingly subtle. The natural history of acute severe AR is
one of LV failure and death in the absence of rapid intervention. Medical Management
Patients with chronic AR may present acutely with a sudden
worsening of their underlying pathology. Acute severe AR has a high mortality rate. Medical man-
agement should not delay urgent or emergent surgery. Con-
gestive heart failure and cardiogenic shock are the principle
Physical Examination targets of acute medical therapies. Use of vasodilators, partic-
ularly sodium nitroprusside, and diuretics are the mainstays
The classic eponymous signs observed in chronic AR are atten- of medical therapy, if the systemic blood pressure allows [65].
uated or absent in acute AR. Patients are often tachycardic with Inotropes such as dopamine or dobutamine may be used to
low or low-normal blood pressure. Pulse pressure may under- augment cardiac output. Pulmonary edema from acute AR
estimate AR severity in the acute setting. Tachypnea, accessory frequently requires intubation and mechanical ventilation.
muscle use, and hypoxemia are worrisome findings and pul- Intra-aortic balloon counterpulsation (IABP) is strictly con-
monary rales are common. LV apical impulse is not displaced traindicated. Beta-blockers should only be considered in cases
unless prior LV dysfunction was present. The first heart sound of acute aortic dissection. Antibiotics are indicated for IE, but
(S1) is often soft due to premature closure of the mitral valve surgery must not be delayed once heart failure intervenes [24].
from the rapid LV diastolic pressure rise. There is often a low-
pitched systolic ejection murmur from increased flow across
the aortic valve, whereas the diastolic regurgitant murmur is of
Surgical Treatment
grade 1 or 2 intensity and of short duration. A pulse deficit or Surgery is indicated for acute severe AR unless overwhelm-
relative decrease may be appreciated in the setting of AR from ing patient comorbidities dictate otherwise. AVR is most
aortic dissection. commonly performed, but valve repair may be possible in
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Chapter 34: Valvular Heart Disease 335

A B

FIGURE 34.7. Echocardiographic appearance of severe aortic regurgitation. A: Transthoracic echocar-


diogram apical four-chamber view with severe aortic regurgitation from infective endocarditis. Color
Doppler shows ventricular filling from the aorta during diastole. B: Pulse wave Doppler of the descending
thoracic aortic reveals holodiastolic flow reversal consistent with severe aortic regurgitation.

cases of leaflet perforation. Most surgeons favor the use of


homograft material for management of aortic valve/root IE Pathophysiology
given the low reinfection rates with cadaveric tissue. A com-
posite valve-graft conduit may be used when disease dictates Rheumatic fever leads to inflammation and scarring of the mi-
replacement of both the aortic root and valve [66]. Perioper- tral valve, with fusion of the commissures and subvalvular ap-
ative risk depends on age, preoperative LV function, etiology, paratus [67]. Although the initial insult is rheumatic, altered
and urgency of the surgery. Debridement of periaortic abscess flow patterns may lead to calcification and valve deformity,
or aortic root replacement compounds operative risk. leading to a narrow funnel-shaped valve. Calcific degeneration
of acquired mitral valve thickening may also produce MS. The
mitral orifice is normally 4 to 6 cm2 . MS develops when the area
is reduced to less than 2 cm2 so that an elevated left atrioven-
tricular pressure gradient is required to propel blood across the
MITRAL STENOSIS mitral valve. Severe MS is present when the valve area is less
than 1 cm2 and a mean transmitral gradient of more than 10
Widespread use of programs to detect and treat Group A strep- mm Hg is present (Table 34.2). An elevated LA pressure leads
tococcal pharyngitis have reduced the incidence of rheumatic to pulmonary hypertension, exercise intolerance, and eventu-
fever in the developed world, the leading cause of MS [67]. ally right-sided heart failure. Adequate transit time is required
The burden of rheumatic valve disease in the developing world to allow blood to flow across the stenotic mitral valve during
remains considerable and is a significant cause of premature diastole.
death. Most cases of rheumatic MS in the United States are
seen in patients who have recently emigrated from endemic
areas [1]. Symptomatic MS requires mechanical relief of LV in-
flow obstruction. ICU management goals include treatment of Clinical Manifestations
heart failure, rate control of AF, and preparation for valvotomy
or valve replacement surgery. History
MS is a slowly progressive disease with a latent period of up
to two decades between the episode of rheumatic carditis and
symptom onset. Progression of MS in developing countries is
Etiology more rapid and may be associated with recurrent episodes of
rheumatic fever. The typical patient will have an asymptomatic
Rheumatic fever produces valvular inflammation and scar- period with an abnormal physical examination. As MS pro-
ring, though nearly half of patients may not recall history of gresses, lesser stresses precipitate symptoms and the patient
acute rheumatic fever or chorea. Two thirds of patients with becomes limited in daily activities; orthopnea and paroxysmal
rheumatic MS are female and 40% of patients with rheumatic
valvular disease will have isolated MS [68]. Screening TTE in
endemic areas may detect up to 10 times as many cases of TA B L E 3 4 . 2
rheumatic valve disease compared with clinical screening alone
[69]. By contrast, in developed countries, MS is more com- SEVERITY OF MITRAL STENOSIS
monly produced by calcific degeneration of the annulus and
mitral leaflets, congenital abnormalities, or collagen vascular Severity of Valve area Mean gradient PA systolic
diseases such as lupus or rheumatoid arthritis [70]. Atrial myx- stenosis (cm2 ) (mm Hg) pressure (mm Hg)
oma may mimic MS by causing obstruction to LV inflow. The
natural history of MS is often dependent on the patients na- Mild >1.5 <5 <30
tionality: in developing countries, patients tend to be younger Moderate 1.01.5 510 3050
with a more pliable valve, whereas in developed countries, pa- Severe <1.0 >10 >50
tients are older with comorbid conditions [71].
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336 Section III: Cardiovascular Problems and Coronary Care

nocturnal dyspnea develop. Pulmonary edema in previously throughout the mitral apparatus and turbulent LV diastolic in-
asymptomatic individuals may be triggered by tachyarrhyth- flow. Direct planimetry to measure valve area may be difficult
mias (AF), volume overload, fever, anemia, hyperthyroidism, in heavily calcified valves [76]. Continuous wave Doppler can
or pregnancy [72]. Each of these circumstances shortens the be used to estimate the LALV pressure gradient. Estimates of
diastolic filling period and elevates the LALV transvalvular mitral valve area can be made by the pressure half-time tech-
gradient. Development of persistent AF marks a turning point nique or the continuity equation [77]. Careful assessment of
in the patients course, with an accelerated rate of symptom the degree and location of valvular calcification, thickening of
progression. Systemic embolization may be the first clue to the the leaflet and subvalvular apparatus, and leaflet mobility can
presence of MS, irrespective of underlying rhythm [73]. Pa- determine suitability for percutaneous mitral balloon valvulo-
tients may also suffer from hemoptysis due to shunting between plasty (PMBV) [78]. Routine assessment of chamber dimension
the pulmonary and bronchial veins, leading to rupture. Under- and ventricular function should be performed. TEE is required
appreciated calcific MS may also be identified after failure to to exclude LA thrombus in patients being considered for PMBV.
wean from mechanical ventilation.
The overall 10-year survival with untreated MS is 50% to Cardiac Catheterization
60% [74]. Asymptomatic patients have a survival of more than
80% at 10 years, whereas symptomatic MS led to death within Catheterization may be necessary to determine stenosis sever-
2 to 5 years in the era before the development of mitral valvo- ity when noninvasive and clinical data are discordant or as
tomy [75]. Once pulmonary hypertension develops, mean sur- a prelude to PMBV (Fig. 34.8). Cardiac output and mean
vival is less than 3 years. Common causes of death associated transvalvular gradient measurements are used to calculate mi-
with MS are heart failure, systemic embolism, and infections, tral valve area using the Gorlin formula [23].
including endocarditis.

Physical Examination Intensive Care Unit Management


MS produces signs of heart failure, including pulmonary rales, Medical Therapy
peripheral edema, ascites, an elevated jugular venous pressure,
and congestive hepatomegaly. Patients with severe MS may also Acute MS typically manifests as pulmonary edema. Reversible
have a malar flush with pinched and blue facies. The first heart precipitants must be identified, such as rapid AF, anemia, sepsis,
sound (S1) is usually accentuated in the early phases of the dis- volume overload, or thyrotoxicosis. Medical therapy is directed
ease. The opening snap (OS) of MS is best appreciated in early at rate control of AF and alleviation of pulmonary and sys-
diastole during expiration near the cardiac apex. The time inter- temic congestion by loop diuretics. Nodal blocking agents such
val between aortic valve closure (A2) and OS varies inversely as beta-blockers or calcium-channel blockers are the preferred
with the severity of MS and the height of LA pressures. The rate controlling agents and may be administered intravenously
OS is followed by a low-pitched rumbling diastolic murmur [79]. Cardioversion may be required in the acute setting to
best heard at the apex with the patient in the left lateral decu- restore hemodynamic stability, though most patients respond
bitus position. Presystolic accentuation of the murmur may be to rate control. Anticoagulation should be initiated promptly.
present in sinus rhythm. In general, the duration of the murmur In patients with only mild-to-moderate MS, addressing one or
corresponds to the severity of stenosis. If the valve is heavily more underlying precipitants will suffice without the need for
calcified and immobile, with low cardiac output or AF, it may mechanical intervention. Patients with severe MS have a poor
be relatively silent with a soft S1, absent presystolic accen- prognosis without intervention, which may consist of PMBV,
tuation, and an inaudible diastolic rumble. Associated valvular surgical commissurotomy, or mitral valve replacement (MVR)
lesions, including the murmurs of AR, pulmonic regurgitation (Fig. 34.9).
(PR), and tricuspid regurgitation (TR), may be present, along
with a loud P2 from pulmonary hypertension or a parasternal Percutaneous Mitral Balloon Valvuloplasty
lift from right ventricle (RV) pressure or volume overload. PMBV is the preferred treatment for symptomatic (NYHA
Class IIIV) patients with isolated severe MS (valve area is
<1 cm2 ) and favorable valve morphology. Unlike PABV, PMBV
Investigations has achieved durable results. Ideal patients for PMBV are
younger (age <45 years), have better NYHA functional class,
Electrocardiogram and have pliable mitral leaflets [80]. PMBV is performed by
transseptal puncture, passing a guidewire across the mitral
The ECG in sinus rhythm may reveal LA enlargement but AF valve, and inflating a balloon (Inoue balloon) across the mitral
can be present at any stage in the natural history. A vertical QRS orifice to split the commissures and widen the stenotic valve
axis may be present along with nonspecific ST-segment and T- [43,81].
wave abnormalities. Signs of RV hypertrophy signify advanced Successful PMBV doubles the mitral valve area, reduces
disease. mean transmitral gradient by half, and improves symptoms
without development of significant MR [82]. Acute complica-
Chest Radiograph tions of PMBV include severe MR; residual atrial septal defect
Radiographic changes with MS include LA enlargement, dila- after transseptal puncture; and, less commonly, LV perforation,
tion of the main pulmonary artery and its central branches, RV cardiac tamponade, and systemic emboli. Overall procedural
enlargement, and signs of pulmonary vascular congestion. In- morality is between 0.4% and 3.0% [83]. Patients have ex-
terstitial or alveolar edema signifies a marked and often acute cellent event-free survival after PMBV with rates of 80% to
elevation of pulmonary capillary wedge (PCW) pressure. 90% over 3 to 7 years when performed by a skilled opera-
tor in a high-volume center [84]. Short- and intermediate-term
outcomes after PMBV are comparable with those after open
Echocardiography surgical commissurotomy, but with reduced morbidity and at
Rheumatic MS is characterized by thickened mitral leaflet tips, lower cost [85]. There is a significant rate of restenosis after
immobility of the posterior leaflet, and restricted anterior leaflet both percutaneous and surgical commissurotomy with most
motion. Calcific MS is marked by dense echogenic deposits patients requiring a repeat procedure within 10 to 15 years.
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Chapter 34: Valvular Heart Disease 337

0.5 sec to treat concomitant AF, though success rates are relatively
ECG lower in rheumatic MS patients. The average operative risk for
MVR is 5%, with an overall 10-year survival in surgical sur-
vivors of 70%. Long-term prognosis is influenced by patient
age, comorbid conditions, and the presence of concomitant
pulmonary hypertension and RV dysfunction.
PRESSURE (mm Hg)

SEP
MITRAL REGURGITATION
Acute, severe MR presents with pulmonary edema and hemo-
dynamic compromise because of the lack of time for the car-
100
diopulmonary circuit to adapt to the additional volume load.
Ao Examination findings may be subtle and presentation may be
mistaken for other acute conditions such as pneumonia or non-
valvular decompensated heart failure. A high clinical index of
suspicion, timely evaluation by TTE, and prompt referral for
LV surgical consultation are of critical value in the management
PCW of this condition [52]. Many patients in the ICU will have MR
accompanied by reduced LV systolic function, from either MI
0 or chronic cardiomyopathy. The management of patients with
A DFP MR and advanced systolic heart failure remains controversial.

ECG Etiology
MR may be caused by abnormalities of any component of the
mitral apparatus: annulus, valve leaflets, chordae tendineae,
papillary muscles, and adjacent LV free wall [87] (Table
100 34.3). Common causes of acute MR include chordal rupture
from myxomatous degeneration, blunt trauma, or endocardi-
tis; leaflet perforation from endocarditis or leaflet avulsion
PRESSURE (mm Hg)

from trauma; papillary muscle infarction with rupture or dis-


placement from acute or chronic ischemia and LV remodeling;
PCW acute rheumatic carditis or other acute condition like stress car-
diomyopathy; and mitral prosthetic paravalvular leak [8890].
Often, the causes of MR are divided into organic disorders
involving the mitral valve leaflets and functional disorders
50 due to tethering of the mitral apparatus from ventricular re-
modeling, LV dilatation, and increased sphericity. This classi-
fication emphasizes when attention should be directed toward
mitral valve surgery (organic causes) or to addressing an un-
derlying cardiomyopathy (functional causes).
Ischemic MR refers to MR produced after acute MI and,
LV more commonly, in chronic ischemic cardiomyopathy. The
most important mechanism of ischemic MR is mitral valve
leaflet tethering due to chronic postinfarction remodeling, re-
0 sulting in apical and lateral displacement of the papillary mus-
cles. This shape change occurs after an inferior or posterior
0.5 sec transmural MI leads to displacement of the posteromedial pap-
B
illary muscle [91]. After MI, the presence of MR can augment
FIGURE 34.8. Hemodynamic measurements in mitral stenosis. A: De- postinfarction remodeling, further exacerbating the degree of
picts normal left ventricle (LV), left atrial (LA), and aortic (Ao) pressure functional MR [92]. Papillary rupture is a rare complication of
tracings. B: Depicts the pressure gradient between pulmonary capillary acute MI (1% to 3%) with a bimodal peak at 1 day, then 3 to 5
wedge (PCW) pressure and LV in a patient with MS (shaded area). days post-MI. The posteromedial papillary muscle has a single
DFP, diastolic filling period; SEP, systolic ejection period. [Adapted blood supply from the right coronary or left circumflex artery,
from Carabello BA: Modern management of mitral stenosis. Circula-
tion 112(3):432437, 2005, with permission.]
and thus is 6 to 10 times more likely to rupture than the an-
terolateral papillary, which has a dual blood supply. Dynamic
MR can occur during episodes of transient ischemia involving
the papillary muscles but is not usually severe [93]. Dynamic
Surgical Treatment MR is also a feature of HOCM and has been described in some
If the anatomy is unfavorable for PMBV or the procedure is un- patients with stress cardiomyopathy.
successful, open surgical valvotomy may be performed, which
requires cardiopulmonary bypass [86]. MVR is necessary in
patients with MS and significant MR and those in whom valve Pathophysiology
anatomy is too distorted to respond to commissurotomy alone.
MVR is often performed with preservation of the chordal at- In acute MR, the LV ejects blood into a small, noncompli-
tachments to facilitate LV recovery. A surgical MAZE proce- ant LA leading to a rapid rise in LA pressure during systole.
dure or isolation of the pulmonary veins may also be performed The difference in LA compliance explains why chronic MR
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338 Section III: Cardiovascular Problems and Coronary Care

Mitral stenosis
presenting acutely

Diastolic rumble
Loud S1
Opening snap

Establish correct diagnosis


TTE/TEE

Pulmonary edema Severe Advanced severe


in noncritical MS edematous MS calcified MS

AF FIGURE 34.9. Management of the


Thyrotoxicosis No Pliable valve acute presentation of mitral steno-
Fluid overload MR < grade II sis (MS). AF, atrial fibrillation; LA,
Pregnancy MVR left atrial; MR, mitral regurgitation;
Yes MV, mitral valve; MVR, mitral valve
MVR Yes
Manage as replacement; PMBV, percutaneous
LA thrombus?
indicated mitral balloon valvuloplasty; S1, first
Anticoagulate 3 months heart sound; TEE, transesophageal
then repeat TEE echocardiography; TTE, transthoracic
No echocardiography. [Adapted from Bel-
lamy MF, Enriquez-Sarano M: Valvular
Yes Thrombus absent? No heart disease, in Irwin RS, Rippe
JM (eds): Intensive Care Medicine.
Philadelphia, Lippincott Williams &
PBMV MV repair Wilkins, 2003, pp 313328, with
permission.]

TA B L E 3 4 . 3 (increased compliance) can be well tolerated and why acute MR


(reduced compliance) is not. The rise in LA pressure is trans-
CAUSES OF ACUTE SEVERE NATIVE MITRAL mitted to the pulmonary venous bed and leads to pulmonary
REGURGITATION edema, which may be asymmetric if there is an eccentric jet of
MR directed to a particular pulmonary vein. The severity of
Mitral annulus disorders pulmonary edema may be relatively less in patients whose LA
Infective endocarditis (abscess formation) has been conditioned by some degree of chronic MR. Large
Trauma (valvular heart surgery) V waves are typically inscribed in the LA and PCW tracings
Paravalvular leak due to suture interruption (surgical during ventricular systole in acute MR [94]. Such V waves
technical problems or infective endocarditis) may also be seen in other conditions, including LV failure and
Mitral leaflet disorders acute ventricular septal rupture. During acute MR, LV systolic
Infective endocarditis (perforation or interfering with valve function may be normal, hyperdynamic, or reduced depending
closure by vegetation) on the etiology of MR. Tachycardia may temporarily preserve
Trauma (tear during percutaneous balloon mitral forward cardiac output, but hypotension, organ failure, and
valvuloplasty or penetrating chest injury) cardiogenic shock may evolve.
Tumors (atrial myxoma)
Myxomatous degeneration
Systemic lupus erythematosus (Libman-Sacks lesion)
Clinical Manifestations
Rupture of chordae tendineae
Idiopathic (spontaneous) History
Myxomatous degeneration (mitral valve prolapse, Marfan
syndrome, Ehlers-Danlos syndrome) In acute severe MR, symptoms of left heart failure predomi-
Infective endocarditis nate, including dyspnea, orthopnea, and cough. Patients with
Acute rheumatic fever post-MI papillary muscle rupture or ischemic MR may have
Trauma (percutaneous balloon valvuloplasty, blunt chest concurrent angina, dyspnea, and abrupt hemodynamic com-
trauma) promise. Spontaneous chordal rupture in myxomatous degen-
eration may be accompanied by chest pain in nearly half of pa-
Papillary muscle disorders tients. Symptoms of fevers, chills, malaise, and anorexia may
Coronary artery disease (causing dysfunction and rarely be present in patients with endocarditis. Trauma is usually self-
rupture) evident (Table 34.4).
Acute global left ventricular dysfunction
Infiltrative diseases (amyloidosis, sarcoidosis)
Trauma Physical Examination
Bonow R, Braunwald E: Valvular heart disease, in Zipes D, et al. (eds): Patients with acute severe MR are tachycardic and tachypneic.
Braunwalds Heart Disease. Philadelphia, Elsevier Saunders, 2005, Blood pressure is variable, though pulse pressure is often nar-
pp 15531621. row due to reduced forward stroke volume. Jugular venous
pressure may be normal or elevated. Rales or wheezes may be
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Chapter 34: Valvular Heart Disease 339

TA B L E 3 4 . 4
CLINICAL FINDINGS IN ACUTE SEVERE MITRAL REGURGITATION

Acute organic MR Papillary muscle rupture Functional MR with CHF

Etiology Ruptured chordae, endocarditis, 1 or 35 d post-MI Ischemic heart disease, dilated


trauma cardiomyopathy
Presentation Acute pulmonary edema Sudden onset pulmonary edema CHF and pulmonary edema
and cardiogenic shock
Clinical Examination
Point of maximum Normal or displaced thrill Usually normal if no Displaced
impulse/apex beat prior LV dysfunction
Murmur Holosystolic loud May be very soft or absent Early systolic, rarely holosystolic
soft
Sounds Third heart sound, second Decreased sounds Third heart sound
heart sound split
Investigations
Electrocardiogram Normal Acute MI Left bundle branch block
Chest radiograph Normal heart size Usually normal Cardiomegaly
Echocardiogram
Two-dimensional LV and LA size normal Normal LV LV and LA dilated
Ruptured chord Ruptured head of Annular dilatation
papillary muscle Tenting of mitral valve leaflets
Doppler Pulmonary venous flow reversal Unimpressive color Restrictive filling
Quantitation Large regurgitation volume Free-flow MR Variable regurgitation volume
Large effective regurgitation Dynamic effective regurgitation
orifice orifice

CHF, congestive heart failure; LA, left atrial; LV, left ventricular; MI, myocardial infarction; MR, mitral regurgitation.
From Parikh S, OGara PT: Valvular heart disease, in Rippe JM, Irwin RS (eds): Intensive Care Medicine. Philadelphia, Lippincott Williams & Wilkins,
2006.

audible over the lung fields and may be asymmetric. The pre- the acute phase. With post-MI papillary muscle rupture, evi-
cordium is often hyperdynamic with a palpable apical thrill. dence of an evolving inferior-posterior or lateral MI may be
S1 is normal or decreased in intensity, whereas S2 may be seen.
widely split due to early closure of the aortic valve. A diastolic
filling complex may be appreciated and consists of a third heart
sound (S3) and a short mid-diastolic rumble from increased Chest Radiograph
transmitral diastolic flow. The systolic murmur of acute MR In acute MR, the cardiac silhouette is normal in size despite
may be highly variable, and even absent in up to half of cases of the present of alveolar pulmonary edema. Asymmetric edema
post-MI papillary muscle rupture. The murmur of acute MR is may be present in patients with a flail leaflet producing an
usually not holosystolic but rather early to mid-systolic in tim- eccentric MR jet, particularly in the right upper lobe [95]. De-
ing, with a crescendodecrescendo configuration, and is coarse compensated chronic MR may have associated cardiomegaly,
rather than high pitched. These features reflect the rapid LA LA enlargement, and prominent pulmonary arteries.
pressure rise and diminution of the LVLA pressure gradient
throughout systole. The murmur of chronic MR, in contrast,
is holosystolic (plateau) due to the persistent LVLA gradient Echocardiography
during systole. The murmur of acute MR is usually loudest at
Prompt TTE is the most important study for patients with
the left sternal border or apex, and the direction of radiation
suspected acute MR (Fig. 34.10). TTE can delineate mitral
may provide a clue as to etiology. Anterior leaflet prolapse or
anatomy, characterize severity, and document underlying LV
flail produces a posterior-lateral regurgitant jet, so the mur-
function and coexisting valvular pathology. Flail leaflet may be
mur typically radiates to the axilla and back. With posterior
diagnosed by rapid movement of a portion of leaflet/chordal
leaflet involvement, the jet is anterior-medial in direction, so the
tissue posteriorly in to the LA during systole. Chordal rupture,
murmur is transmitted to the base, where it may be confused
leaflet vegetations, and periannular abscess may be identified
with AS.
in endocarditis. In patients with functional MR, LV remod-
eling may be evident along with annular dilatation, papillary
muscle displacement, and leaflet tethering. Semiquantitative as-
Investigations sessment of MR severity can be performed with color flow
and continuous wave Doppler interrogation. MR severity cor-
relates with LA jet width area, pulmonary vein systolic flow
Electrocardiogram reversal, effective regurgitant orifice area, and regurgitant frac-
ECG may show sinus tachycardia or an atrial arrhythmia, tion and volume [96,97]. These semiquantitative measures are
such as AF. LA abnormality may be discernible if P waves are less important as guides for acute decision making but remain
present, though signs of LV chamber enlargement are rare in important for longitudinal management (Table 34.5). TEE can
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340 Section III: Cardiovascular Problems and Coronary Care

A B

FIGURE 34.10. Mitral regurgitation. A: Color-flow Doppler image from the apical four-chamber view
of a patient with myxomatous degeneration of the mitral valve with posterior leaflet prolapse producing
an anteromedially directed jet of severe mitral regurgitation against the interatrial septum. Eccentric jets
are common in prolapse and/or flail leaflet and are directed opposite the involved leaflet. B: The V
wave of mitral regurgitation. This hemodynamic tracing shows a large left atrial V wave (arrowheads)
occurring during ventricular systole in a patient with atrial fibrillation (A wave absent). Following
the V wave, there is a rapid fall in left atrial (LA) pressure, along the course of the declining left
ventricular (LV) pressure. In diastole, LA and LV pressures are equalized. The arrow indicated the C
wave deflection. Giant V waves are defined by an increase in >10 mm Hg above mean pressure and are
consistent with mitral regurgitation, but may be blunted in patients with large and compliant left atria.
ECG, electrocardiogram. [From OGara PT: Valvular heart disease, in Libby P (ed): Essential Atlas of
Cardiovascular Disease. New York, NY, Springer, 2009, p 216, Figures 920 and 922.]

further characterized mitral anatomy and MR severity if TTE


images are suboptimal or complicated IE is suspected. Intensive Care Unit Management
Medical Therapy
Cardiac Catheterization The goal of medical therapy for acute severe MR is to stabi-
Catheterization is rarely required to define MR etiology or lize the patient in anticipation of surgery for definitive treat-
severity. If there is a discrepancy between clinical findings and ment. Afterload reduction with intravenous vasodilators is the
noninvasive imaging or when estimated pulmonary artery pres- mainstay of acute medical therapy, as systolic blood pressure
sures are out of proportion to the degree of MR, then inva- tolerates. Sodium nitroprusside infusion is preferred, though
sive hemodynamic assessment is indicated. MR severity may extended use requires monitoring of thiocyanate levels [65]. In-
be qualitatively assessed by contrast ventriculography. Coro- otropes such as dobutamine or dopamine may occasionally be
nary angiography typically precedes surgery for patients with required to support cardiac output and arterial pressure. IABP
coronary risk factors and in those with suspected post-MI pap- for mechanical afterload reduction may be particularly helpful
illary rupture or dynamic, ischemic MR. in reducing regurgitant volume and decreasing LV end-diastolic
pressure. If end-organ hypoperfusion or hypotension indicates
that cardiogenic shock is present, IABP should be promptly ini-
tiated as a bridge to the operating room. Loop diuretics may
help ameliorate pulmonary edema.
TA B L E 3 4 . 5
Adjunctive medical therapy is driven in part by suspected
ECHOCARDIOGRAPHIC FINDINGS CONSISTENT etiology. Antibiotics are indicated for IE and anti-ischemic ther-
WITH SEVERE MITRAL REGURGITATION apy is required for post-MI papillary muscle rupture [98]. With
medical therapy alone, the mortality after papillary rupture is
Qualitative 80% [99]. Although percutaneous coronary intervention (PCI)
Vena contracta width >0.7 cm with large central MR jet may help relieve MR in the setting of acute MI, severe MR
(area >40% left atrial area) or with a wall-impinging jet will most often require surgical correction despite successful
of any size, swirling in left atrium (Echo, Doppler) coronary reperfusion. Despite recent advances in percutaneous
Pulmonary vein systolic flow reversal (Doppler) valve repair techniques, none has yet been tested in the setting
Dense contrast in left atrium (angiography) of acute MR [100,101]. Similarly, cardiac resynchronization
therapy (CRT) may help reduce chronic, functional MR re-
Quantitative
lated to contractile dyssynchrony but has no role in the acute
Regurgitant volume 60 mL per beat
setting [102]. Surgical planning should not be delayed, but an
Regurgitant fraction 50%
operation may have to await improvement in organ function
Effective regurgitant orifice 0.40 cm2 after the measures described above are instituted.
From Zoghbi WA, Enriquez-Sarano M, Foster E, et al:
Recommendations for evaluation of the severity of native valvular Surgical Therapy
regurgitation with two-dimensional and Doppler echocardiography.
J Am Soc Echocardiogr 16:777802, 2003, with permission. Surgery is indicated for the treatment of acute severe MR. In
contrast to acute severe AR, many patients with acute severe
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Chapter 34: Valvular Heart Disease 341

MR may be stabilized over the course of several days with TR is targeted at the underlying disease process and reversing
IABP or inodilators to allow operation under less urgent cir- secondary causes of pulmonary hypertension [110]. For exam-
cumstances [24]. Also unlike acute AR, acute severe MR may ple, with LV failure, appropriate management with diuresis and
be treated with either repair or replacement. Valve repair is the afterload reduction with vasodilators may reduce the degree of
preferred surgical therapy when possible [103]. Mitral repair functional TR. When caused by left-sided heart disease, wors-
involves valve reconstruction using a variety of valvuloplasty ening TR can be a marker of underlying RV compromise and
techniques and insertion of an annuloplasty ring. In addition heralds a poor prognosis [111]. Secondary TR caused by mitral
to reducing the need for anticoagulation and the risk of late valve disease is increasingly addressed with annuloplasty repair
prosthetic valve failure, valve repair preserves the integrity of at the time of mitral valve surgery, since functional TR occur-
the subvalvular apparatus, which maintains LV function to a ring late after a left-sided valve operation is associated with
greater degree. Valve repair using an undersized annuloplasty high morbidity and mortality [112]. Tricuspid annuloplasty or
ring is more likely to be used for ischemic MR [52]. Valve valve replacement surgery may also be required for severe pri-
replacement with chordal sparing is needed when there is de- mary TR causing worsening RV systolic function or refractory
struction, distortion, or infection of the native tissue that makes right heart failure.
repair impossible. Surgical strategy is often guided by intraop-
erative TEE and direct visual inspection after the patients is
placed on cardiopulmonary bypass.
Surgical outcome depends on age, underlying LV function, PROSTHETIC VALVE
the presence of concomitant coronary disease, patient comor-
bidities, and the etiology of MR [104]. IE has a high mortality
DYSFUNCTION
rate even with medical and surgical therapy, though mortal- Valve replacement surgery has been a major breakthrough al-
ity has decreased with improvements in operative technique lowing patients with severe valvular heart disease to have bet-
and more widespread use of mitral repair [105,106]. With the ter quality and length of life. Prosthetic valves may be either
addition of bypass grafting to mitral valve repair, operative mechanical or bioprosthetic (Fig. 34.11). The choice of pros-
mortality in patients with ischemic MR is now less than 10% thesis is informed by patient age, the need for anticoagula-
[99,107]. tion, hemodynamic profile, durability, and patient preference
The surgical approaches to patients with MR accompanied [113]. Mechanical valves have excellent durability and hemo-
by advanced systolic heart failure continue to evolve and re- dynamic performance but require life-long anticoagulation to
main controversial [108]. There is broad consensus that pa- prevent thromboembolic complications [114]. In contrast, the
tients with chronic MR and heart failure should be optimized principal advantage of bioprosthetic valves is the virtual ab-
on medical therapy, evaluated for revascularization if coronary sence of thromboembolic complication after 3 months, ex-
disease is present, and provided with CRT if the EF is less cept when there are risk factors such as a hypercoagulable
than 35% and a wide QRS, left bundle branch block com- state or chronic AF with atrial enlargement [115]. Biopros-
plex (>120 milliseconds) is present. After these steps, recon- thetic valves are usually xenografts (porcine or cryopreserved,
firmation of MR severity is required before considering MV mounted bovine pericardium); homografts from human cadav-
surgery. If severe MR is present, a careful integrated assess- ers are used to treat aortic valve and root endocarditis. All bio-
ment of LV reverse remodeling viability (usually with cardiac prostheses are at risk for structural valve deterioration (SVD),
magnetic resonance imaging), mitral apparatus geometry, and which is mostly a function of age at implant. SVD occurs more
patient comorbidities must be made in consultation with car- rapidly among patients younger than 40 years compared with
diology and cardiac surgery colleagues [108]. As percutaneous those older than 65 years. Rates of SVD may not differ between
and less invasive approaches to mitral valve disease in patients homograft and xenograft valves. Over the past 10 years, there
with heart failure continue to evolve, ongoing clinical trials has been a trend toward using bioprosthetic valves in relatively
will help refine the selection of candidates for mitral surgery younger patients (ages 50 to 65 years) despite the inherent risk
and determine outcomes of mitral repair versus chord-sparing of SVD and need for reoperation, given the increased durabil-
replacement. ity of the current generation xenograft valves, decreased risk at
reoperation, aggregate risks of long-term anticoagulation, and
patient lifestyle preferences.
TRICUSPID REGURGITATION All prosthetic valves are subject to dysfunction that can
lead to significant hemodynamic compromise. Common pros-
Most ICU patients with TR have functional regurgitation thetic valve abnormalities include mechanical valve thrombosis,
rather than a primary valvular abnormality. Functional TR prosthetic valve endocarditis (PVE), structural deterioration
is produced when the tricuspid annulus is dilated due to RV and failure, and paravalvular regurgitation with or without
infarction, congenital heart disease, or pulmonary hyperten- hemolysis. For patients with a prosthetic valve admitted to the
sion with RV dilatation, often secondary to chronic left heart ICU, management focuses on appropriately excluding pros-
failure. TR is often present in patients with chronic left-sided thetic valve dysfunction using TTE and TEE when required
valve disorders that produce secondary pulmonary hyperten- and maintaining optimal prosthetic valve function [116].
sion or with pathologic processes affecting multiple valves,
such as rheumatic disease, endocarditis, or myxomatous degen-
eration [109]. The most important causes of primary valvular
TR are trauma and IE, particularly in patients who abuse intra- Prosthetic Valve Thrombosis
venous drugs. When severe, TR may contribute to symptoms
of right heart failure, including fatigue, edema, and ascites. The Prosthetic valve thrombosis (PVT) is any valve thrombus at-
murmur of TR usually increases in intensity with inspiration tached to or near an operated valve that occludes part of the
(Carvallos sign). Examination of the neck veins reveals large blood flow path or interferes with the function of the valve
V-waves. A pulsatile liver edge may also be felt in the right [32]. PVT is a rare but life-threatening condition (Fig. 34.12).
upper quadrant. It is more common with older generation mechanical valves,
Despite the significant volume load imposed by severe TR, particularly in the setting of inadequate anticoagulation. The
the RV tolerates TR remarkably well and operation is rarely in- incidence is estimated to be between 0.3% and 1.3% per year
dicated in the absence of other valve disease [32]. Therapy for in patients with mechanical valves [117,118].
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342 Section III: Cardiovascular Problems and Coronary Care

A B C D

G
E F H

FIGURE 34.11. Different types of prosthetic heart valves. A: Bileaflet mechanical valve (St. Judes);
B: monoleaflet, tilting disk mechanical valve (Medtronic Hall); C: caged ball valve (Starr-Edwards);
D: stented porcine bioprosthesis (Medtronic Mosaic); E: stented pericardial bioprosthesis (Carpentier-
Edwards Magna); F: stentless porcine bioprosthesis (Medtronic Freestyle); G: percutaneous bioprosthesis
expanded over a balloon (Edwards Sapien); H: self-expandable percutaneous bioprosthesis (CoreValve).
[From Pibarot P, Dumesnil JG: Prosthetic heart valves: selection of the optimal prosthesis and long-term
management. Circulation 119:10341048, 2009, with permission.]

Clinical Presentation and Investigations more insidious with caged-ball valves and more abrupt with
tilting disk valves [120]. The physical examination may be un-
PVT follows a rapid clinical course, unlike the in-growth of
revealing, though soft mechanical valve closure sounds or a
fibrous/pannus tissue within a prosthetic valve ring, which
pathologic murmur may be present.
slowly gives rise to valve dysfunction and stenosis [119]. PVT
A subtherapeutic international normalized ratio (INR) in
manifests as abrupt onset of systemic embolization, conges-
a patient with a mechanical valve is a red flag for PVT
tive heart failure, or cardiogenic shock. The degree of hemody-
[121]. Rapid diagnosis depends on prompt TTE or fluoroscopy,
namic compromise is determined by valve position and degree
though both modalities may be complementary [122]. TTE
of resulting dysfunction. In general, the time course may be
can diagnose the presence of valve thrombus, its composition,
and associated functional stenosis or regurgitation. TEE usu-
ally provides further risk stratification, particularly in cases of
suspected mitral PVT and when TTE windows are inadequate
[123]. Fluoroscopy can be useful to characterize caged-ball,
tilting-disc, or bileaflet mobility. Excursion of tilting-disc me-
chanical valves is much better appreciated with fluoroscopy
than with TTE.

Intensive Care Unit Management


Initial management should focus on systemic anticoagulation
with intravenous heparin to prevent thrombus extension. Small
thrombi without hemodynamic compromise are often treated
with anticoagulation alone, whereas larger thrombi require ei-
ther fibrinolytic therapy or surgery [24,37]. Fibrinolytic ther-
apy is associated with risks of life-threatening hemorrhage and
systemic embolization and thus is often delivered in the ICU for
purposes of monitoring. The latter risk is low with right-sided
PVT and higher with left-sided PVT, with a risk of cerebral
embolism of 12% to 15% [124,125]. Fibrinolysis is consid-
ered first-line therapy for patients with right-sided PVT and for
those with left-sided PVT, a small thrombus burden or NYHA
Class III symptoms [32]. Fibrinolysis is less useful and po-
FIGURE 34.12. Prosthetic valve thrombosis in a bileaflet mitral valve. tentially more harmful if LA thrombus is present, if the valve
[From Goldsmith I, Turpie AGG, Lip GYH: ABC of antithrom- thrombus is older than 2 weeks, or if PVT is accompanied by
botic therapy: valvar heart disease and prosthetic heart valves. BMJ shock. TTE after fibrinolysis can monitor for thrombus resolu-
325(7374):12281231, 2002, with permission.] tion and dictate the need for additional fibrinolysis for residual
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 34: Valvular Heart Disease 343

thrombus [126]. Alteplase is the most commonly used fibri- signs of PVE including vegetations, paraprosthetic abscess, or
nolytic for PVT, though urokinase and streptokinase have also new paravalvular regurgitation [131].
been used. After successful fibrinolysis, unfractionated heparin Eradication of the infecting pathogen with antimicrobial
should be initiated along with warfarin until an INR of 3.0 to therapy alone is often impossible and depends on the virulence
4.0 is achieved in patients with a prosthetic aortic valve or an of the organism and extent of infection. Medical therapy is
INR of 3.5 to 4.5 for a prosthesis in the mitral position [24]. more likely to be successful with late PVE or in nonstaphylo-
Emergency operation is recommended for patients with coccal bacterial infections [132]. Surgical consultation should
hemodynamic instability, NYHA Class IIIIV symptoms, or be sought early in the course of PVE. Indications for surgical
a large clot burden as defined by TEE (>0.8 cm2 ) [32,37]. Pe- therapy include failure of medical treatment marked by persis-
rioperative mortality rates approach 15% and are highest for tent bacteremia, hemodynamically significant prosthesis regur-
PVT in the mitral position. A bioprosthesis is recommended gitation with LV dysfunction, large vegetations, paravalvular
after PVT to reduce future risk of valve thrombosis. extension with abscess or conduction defects, or development
of intracardiac fistulas [32]. Surgery is almost always required
in cases of S. aureus PVE. Infection with S. aureus is a marker
Prosthetic Valve Endocarditis for hospital mortality.

The incidence of PVE is 0.5% per year even with appropriate


antibiotic prophylaxis and accounts for 7% to 25% of all cases Structural Valve Deterioration
of endocarditis in the developed world [54]. Endocarditis of a
prosthetic valve is a devastating disease that carries a mortal- Failure of mechanical valves in the absence of infection is rare.
ity rate of 30% to 50%. This high mortality reflects not only Mechanical failure from strut fracture often presents with dys-
more serious infection but also the difficulty eradicating infec- pnea, acute heart failure, and hemodynamic collapse with a
tion with antibiotics alone [127]. Infection may involve any physical examination marked by absent valve clicks. Death
part of the valve prosthesis, but the sewing ring may be partic- from mechanical valve strut fracture ensues rapidly if the valve
ularly vulnerable. Sewing ring infection may result in abscess is in the aortic position; patients with mitral valve failure can
formation, paravalvular regurgitation, and further penetration often be stabilized prior to surgery.
into adjacent cardiac structures. The risk of PVE may be higher With conventional stented bioprostheses, freedom from
with mechanical valves in the first few months after implanta- SVD is 70% to 90% by 10 years, and 50% to 80% at 15 years
tion, but long-term risk is similar for mechanical and biopros- [133,134]. SVD of bioprostheses is often related to tearing or
thetic valves [53]. Infection with coagulase-negative staphylo- rupture of one prosthetic valve cusp or progressive calcification
cocci is common within the first postoperative year; S. aureus and immobility [135]. Risk factors for SVD include younger
and streptococci species dominate in later years [128130]. age at implant, mitral valve position, renal insufficiency, and
Fever is the most common symptom and may be associated hyperparathyroidism [136]. Evaluation for SVD requires TTE
with other signs of prosthetic valve dysfunction including con- and often TEE with care to exclude endocarditis as a com-
gestive heart failure, a new murmur, or embolic phenomena. plicating feature. SVD is the most common cause of reopera-
Blood cultures are crucial and should be drawn prior to antibi- tive valve replacement in patients with a bioprosthesis. Indi-
otic therapy in any patient with a fever and a prosthetic valve. cations for reoperation are similar for those with native valve
TEE is essential because of its greater sensitivity in detecting disease and are dominated by the development of heart failure.

TA B L E 3 4 . 6
ADVANCES IN VALVULAR HEART DISEASE

Transcatheter aortic valve implantation for advanced calcific AS has been safely performed in select centers and is being studied
in multiple clinical trials [4749]. It will likely become available for clinical use in high-risk AVR patients with severe AS.
Given the incremental risk conferred by coronary artery bypass grafting along with valve surgery, hybrid surgical approaches
combining percutaneous coronary intervention with primary or reoperative valve repair/replacement are now being used for
high-risk patients [143].
The natural history of bicuspid aortic valve disease is influenced by age at diagnosis, degree of valvular dysfunction, and aortic
morphology [10]. In patients with bicuspid aortic valves who require valve surgery, careful elucidation of thoracic aortic
morphology by CT angiography or MRI is required for optimal planning [144].
In patients with low-flow, low-gradient AS, significant predictors of poor outcome are impaired functional capacity on 6-minute
walk, severity of AS at a normalized transvalvular flow rate, reduced peak stress LV ejection fraction during dobutamine
echocardiography, multivessel coronary artery disease, and low mean gradient (<20 mm Hg) [26,27,33].
Despite the association between atherosclerosis and calcific valve degeneration, intensive lipid lower therapy has failed to halt the
progression of calcific AS in multiple randomized clinical trials [7,8].
In developing countries, systematic screening with echocardiography reveals a higher prevalence of rheumatic heart disease
(approximately 10 times as great) compared with clinical screening, raising important public health implications [69].
Endovascular edge-to-edge mitral valve clipping can reduce mitral regurgitation and stimulate reverse remodeling, offering an
alternative to surgical repair for functional mitral valve disease [145].
Novel oral anticoagulants have been developed (e.g., dabigatran, a direct thrombin inhibitor) for use in AF and are being studied
for anticoagulation of mechanical valve prostheses [146].
Transcatheter closure of prosthetic paravalvular leak is being used in select centers [141].
Updated guidelines now recommend that routine antibiotic prophylaxis for infective endocarditis is no longer necessary except in
patients at greatest risk for complications from endocarditis, including those with prosthetic valves or previous endocarditis
[132,147].

AF, atrial fibrillation; AS, aortic stenosis; AVR, aortic valve replacement; CT, computerized tomography; LV, left ventricle; MRI, magnetic resonance
imaging.
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344 Section III: Cardiovascular Problems and Coronary Care

Development of percutaneous valve-in-valve bioprosthesis im- taneous occlusion of the paravalvular leak may be achieved in
plantation is underway and may offer an alternative to reoper- select cases with the use of a septal or ductal occluder device
ation in select high-risk patients [137]. [140,141].

Paravalvular Regurgitation PREVENTING INFECTIVE


ENDOCARDITIS
Paravalvular regurgitation is most often due to infection, su-
ture dehiscence or fibrosis, and calcification of the native an- Emerging data on the lifetime risk of IE, as well as trends in
nulus leading to inadequate contact between the sewing ring antibiotic resistance and antibiotic-associated adverse events,
and annulus. Mild paravalvular regurgitation on periopera- have led to changes in guideline recommendations for antibi-
tive echocardiography has a benign course with reoperation otic prophylaxis [142]. IE is much more likely to occur from
required in less than 1% of patients at 2 years [138]. In pa- frequent exposure to random bacteremias associated with daily
tients with more severe paravalvular leak, close follow-up is activities than from medical or dental procedures. Antibiotic
required and surgical intervention is warranted for those who prophylaxis for IE should only be provided to patients at great-
develop symptoms, progressive LV dysfunction, or hemolysis. est risk for complications from endocarditis, including patients
A large proportion (>50%) of mechanical valve patients have with prosthetic valves, previous IE, complex congenital heart
some degree of mild intravascular hemolysis marked by ane- disease, or cardiac transplantation. Routine antibiotic prophy-
mia and an elevated lactate dehydrogenase. Paravalvular leaks, laxis for mitral valve prolapse is no longer recommended. In
particularly small leaks, can lead to more severe anemia due the ICU, antibiotic prophylaxis may be reasonable for pro-
to shearing of red blood cells. Severe, refractory anemia not cedures involving an infected respiratory, gastrointestinal, or
responsive to iron, folate, and erythropoietin is an indication genitourinary tract [32,132].
for repeat valve operation or closure of the paravalvular leak Advances in valvular heart disease are summarized in
[139]. In high-risk patients not suitable for reoperation, percu- Table 34.6.

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120. Edmunds LH Jr: Thromboembolic complications of current cardiac valvu- and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol
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Chapter 35: Critical Care of Pericardial Disease 347

CHAPTER 35 CRITICAL CARE OF


PERICARDIAL DISEASE
AKSHAY S. DESAI AND KENNETH L. BAUGHMAN

dial volume with trivial increases in intrapericardial pressures.


PERICARDIAL ANATOMY Once this capacitance is exceeded, rapid increases in intraperi-
cardial volume result in steep increments in intrapericardial
The pericardium consists of two layers: the inner layer (visceral pressures, with potentially deleterious consequences for cardiac
pericardium) is a thin, elastic monolayer of mesothelial cells filling and ventricular performance [5,6]. By contrast, gradual
that is tightly adherent to the epicardial surface of the heart, changes in myocardial or pericardial volume (well in excess of
whereas the outer layer (parietal pericardium) is a largely acel- the normal pericardial reserve) may be accommodated with-
lular network of collagen and elastin fibers that make up a out invoking dramatic consequences of pericardial restraint.
thick, stiff fibrous envelope. The visceral pericardium reflects In experimental models of chronic volume overload, the peri-
back near the origins of the great vessels and the junctions of the cardium exhibits the ability to undergo gradual stretch and
caval vessels with the right atrium, becoming continuous with hypertrophy, enhancing its compliance and diminishing its im-
the parietal pericardium and generating a potential space (peri- pact on the ventricular pressurevolume relationship [7]. Such
cardial sac) that is normally lubricated by up to 50 mL of serous chronic stretch is the primary mechanism permitting the accom-
fluid. Most of the heart (excepting a portion of the left atrium) modation of chronic cardiac dilation (as in dilated cardiomy-
and portions of the aorta, pulmonary trunk, pulmonary veins, opathy) or large, slowly accumulating pericardial effusions (as
and venae cavae are contained within this sac, which has lig- in malignant lymphoma), without hemodynamic embarrass-
amentous attachments to the diaphragm, sternum, and other ment (Fig. 35.1).
structures in the anterior mediastinum. The main arterial blood
supply of the pericardium is provided by the pericardiophrenic
artery, a branch of the internal thoracic artery, whereas venous
drainage occurs via pericardiophrenic veins that are tributaries
PERICARDIAL
of the brachiocephalic veins. Sensory enervation is provided by PATHOPHYSIOLOGY
the phrenic nerves with vasomotor innervation from the sym-
pathetic trunks [1,2]. Pericardial manifestations are seen in a wide spectrum of med-
ical and surgical conditions, including a host of infectious,
immune/inflammatory, and neoplastic disorders (Table 35.1).
NORMAL PHYSIOLOGY OF Broadly speaking, from the vantage point of critical care, there
are three conditions to be considered: (i) acute pericarditis,
THE PERICARDIUM (ii) pericardial effusion and tamponade, and (iii) constrictive
pericarditis. We consider the diagnosis, pathophysiology, and
Although an intact pericardium is not critical to the mainte- management of each of these in turn in the discussion to follow.
nance of cardiovascular function, the pericardium does have
several physiologically relevant functions. First, it provides im-
portant structural support for the heart, limiting excessive car-
diac motion within the thoracic cavity during respiration and
Acute Pericarditis
changes in body position. In addition, it acts as a lubricant Pericardial inflammation presents in many clinical settings and
(minimizing friction between the cardiac chambers and the sur- has a wide range of causes. Although pericarditis is classically
rounding structures) and as an anatomic barrier to infection. identified by the clinical triad of acute chest pain, pericardial
Perhaps the best-characterized mechanical function of the nor- friction rub, and characteristic electrocardiographic changes,
mal pericardium, however, is as a restraint on cardiac filling subacute and chronic presentations are also possible. It may
and rapid chamber dilation [3]. At low applied stresses, ap- occur as an isolated entity or as the result of systemic disease;
proximating those at physiologic cardiac volumes, pericardial though most often a strictly inflammatory fibrinous lesion with-
tissue is quite compliant. As the distending pressure increases, out clinically recognizable fluid, sequelae including pericardial
however, it abruptly becomes quite stiff and resistant to further effusion (occasionally progressing to tamponade), pericardial
stress. As a result, the pericardium passively restrains intracar- constriction, or recurrent (relapsing) pericarditis are often seen.
diac volume and limits ventricular filling, with a component of A prevalence of around 1% in autopsy studies suggests that
intracavitary filling pressure reflecting transmitted pericardial pericarditis may frequently be subclinical [8]. Pericarditis is
pressure. In addition, this pericardial restraint defines a total thought to account for around 5% of presentations to emer-
compliance for the system, enhancing ventricular interdepen- gency departments for nonischemic chest pain [9].
dence by accentuating the consequences of septum-mediated
ventricular interactions during diastolic filling [4]. Causes
The pericardium itself has a small capacitance reserve (150
to 250 mL) that admits initial increments in intrapericar- Despite an ever-expanding array of diagnostic techniques, the
vast majority of cases of pericarditis remain idiopathic in eti-
ology [1012]. Even when pericardial fluid or tissue samples
Deceased are obtained, the cause is undefined in up to 30% of patients.
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348 Section III: Cardiovascular Problems and Coronary Care

20
Pressure (mm Hg)

Tamponade
FIGURE 35.1. Pericardial pressure
volume relationship and relationship
to development of pericardial tam-
ponade. The ability of the peri-
10 Limits of pericardial stretch cardium to accommodate pericardial
fluid without hemodynamic embar-
rassment depends heavily on the rate
of fluid accumulation. Note the steep-
ness of the relationship in normal peri-
cardium and the marked flattening
0 and shift to the right with chronic vol-
ume overload. [Adapted from Free-
0 100 200 300 400 500 600
man G, LeWinter MM: Pericardial
Volume (mL) adaptations during chronic cardiac di-
lation in dogs. Circ Res 54:294300,
Acute fluid accumulation Chronic fluid accumulation 1984.]

Broadly speaking, pericarditis is either infectious (two-thirds lization of early reperfusion strategies for acute coronary syn-
of cases) or noninfectious (one-third of cases) in etiology, with dromes (thrombolysis and primary angioplasty).
noninfectious cases attributable to one of a number of im-
mune, neoplastic, traumatic, and metabolic conditions (see Presentation and Diagnosis
Table 35.1). A wide range of organisms cause infectious
Although patients with acute pericarditis may be asymp-
pericarditis, but viral infection remains the most common
tomatic, the typical presentation is with chest pain that is
probable or identifiable cause. Organisms responsible for my-
retrosternal in location, sudden in onset, and exacerbated by
ocarditis are commonly implicated, particularly enteroviruses,
inspiration (pleuritic). The pain may be made worse by ly-
adenoviruses, and influenza; herpes simplex and cytomega-
ing supine and improved by sitting upright and leaning for-
lovirus may also be important in immunocompromised indi-
ward. Precordial distress may closely mimic angina, including
viduals. Myopericarditis has also been reported after smallpox
a predominant pressure sensation with radiation to the neck,
vaccination in US military personnel not previously exposed
arms, or left shoulder. However, radiation of chest pain to
to vaccinia [13]. Although pericardial abnormalities are seen
one or both trapezius muscle ridges favors the diagnosis of
in up to 20% of patients with human immunodeficiency virus
pericarditis because the phrenic nerve, which innervates these
(HIV) infection, symptomatic pericarditis in these patients is
muscles, traverses the pericardium. A prodrome of low-grade
commonly due to secondary infection (e.g., mycobacterial) or
fever, malaise, and myalgia is common, but fever may be ab-
neoplasia (particularly lymphoma or Kaposis sarcoma), and
sent in elderly patients. Associated symptoms can include dys-
the frequency decreases with effective antiretroviral therapy
pnea, cough, anorexia, anxiety, and occasionally, odynophagia
[14]. Bacterial pathogens typically cause purulent pericarditis,
or hiccups.
but are implicated infrequently in pericardial disease, typically
Nearly 85% of patients with pericarditis have an audible
as a consequence of hematogenous seeding or direct extension
friction rub during the course of their disease [12]. Typically,
from adjacent infected tissues (lungs or pleural space) [15].
the rub is a high-pitched scratchy or squeaky sound best heard
Mycobacterium tuberculosis causes up to 4% of acute peri-
at the lower left sternal border or apex at end expiration with
carditis cases and 7% of tamponade presentations in devel-
the patient leaning forward. Classically, it consists of three
oped countries, and remains an important causal factor in
components corresponding to ventricular systole, early dias-
developing nations and immunocompromised hosts [16,17].
tolic filling, and atrial contraction, and has been likened to the
Tuberculosis-related pericarditis can require pericardial biopsy
sound made when walking on crunchy snow. It is distinct from
for diagnosis and is complicated by pericardial effusion or con-
a pleural rub in that it is present throughout the respiratory
striction in up to 50% of cases [18].
cycle, whereas the pleural rub disappears when respirations
In the remainder of patients, pericarditis occurs in conjunc-
are suspended. The pericardial friction rub is often a dynamic
tion with a dissecting aortic aneurysm (in which blood leaks
sound that can disappear and reappear over short periods of
into the pericardial space), after blunt or sharp trauma to the
time. Because of this variable quality, frequent auscultation in
chest, as a result of neoplastic invasion of the pericardium, after
the upright, supine, and left lateral decubitus positions is im-
chest irradiation, in association with uremia or dialysis, after
portant for patients in whom a diagnosis of pericarditis is sus-
cardiac or other thoracic surgery, in association with an inflam-
pected.
matory or autoimmune disorder, or as a result of certain phar-
macologic agents. Iatrogenic cases are increasingly common,
with postpericardiotomy syndrome reported in up to 20% of
Electrocardiogram
patients at a median of 4 weeks following cardiac surgery [19] The electrocardiogram (ECG) is a key diagnostic test in sus-
and symptomatic pericarditis in up to 2% of patients under- pected pericarditis, though typical changes are not always
going percutaneous coronary intervention, catheter ablation seen. The classic finding is widespread, concave ST-segment
procedures, or implantation of active fixation pacemaker or elevation, often with associated PR-segment depression (Fig.
defibrillator leads [10]. Pericarditis associated with acute trans- 35.2). Although the changes may appear regional and therefore
mural myocardial infarction and the delayed immune-mediated mimic myocardial ischemia, reciprocal ST-segment depressions
postinfarction pericarditis of Dresslers syndrome used to be are absent, as are pathologic Q-waves. In addition, the ECG
common, but the incidence has declined with the broader uti- in pericarditis exhibits a typical pattern of evolution that is
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Chapter 35: Critical Care of Pericardial Disease 349

TA B L E 3 5 . 1
ETIOLOGIES OF ACUTE PERICARDIAL DISEASE

Etiology Examples Incidence Treatment

Idiopathica 85%90% Aspirin, NSAIDs


Infectious Echovirus, coxsackievirus, adenovirus, 1%2% Aspirin, NSAIDs
Virala cytomegalovirus, hepatitis B, 1%2% Antibiotics, surgical
Bacteriala EpsteinBarr virus (infectious 4%5% drainage
Mycobacteriala mononucleosis), HIV/AIDS Rare (<1%) Antimycobacterial
Fungal Pneumococcus, Staphylococcus, therapy and
Streptococcus, Mycoplasma, prednisone
Borrelia spp. (Lyme disease), Antifungal therapy,
Haemophilus influenzae, Neisseria drainage
meningitidis, Mycobacterium
tuberculosis, M. avium-
intracellulare, Histoplasma,
Coccidioides
Immune/inflammatory Connective tissue diseasea (systemic 3%5% Aspirin, NSAIDs,
lupus erythematosus, rheumatoid Rare (<1%) glucocorticoids
arthritis, scleroderma) Discontinue drug;
Arteritis (polyarteritis nodosa, aspirin, NSAIDs
temporal arteritis)
Drug induceda (e.g., procainamide,
hydralazine, isoniazid, cyclosporine)
Neoplastic Primary: mesothelioma, sarcoma, etc. 5%7% NSAIDs,
Secondarya : breast carcinoma, lung intrapericardial
carcinoma, lymphoma infusion of
glucocorticoids
Myocardial infarction Early postmyocardial infarction (MI) 5%6% of patients with Aspirin (avoid
related Late postmyocardial infarction transmural MI NSAIDs)
Aortic dissection related (Dresslers syndrome)a Formerly 3%4% of patients Urgent surgery
Proximal aortic dissection with MI, much less in the era (do not drain)
of early reperfusion
Rare (<1%)
Traumatica Blunt and penetrating trauma, NA NSAIDs (avoid
postcardiopulmonary resuscitation aspirin)
Procedure and device Early postcardiac surgery Common Aspirin, NSAIDs
related Post-ICD/pacemaker,a Rare (<1%) Aspirin, NSAIDs
postangioplasty,a late post
cardiotomy or thoracotomy
(Dresslers variant)a
Radiation induceda Chest wall irradiation Rare (<1%) NSAIDs
Uremic or dialysis 5% of patients with chronic Initiate or intensify
associated kidney disease predialysis, dialysis, NSAIDs
13% after dialysis
a
Conditions that manifest as acute pericarditis.

distinct from that of patients with evolving myocardial infarc- myocarditis, or biventricular injury. The entire ECG evolution
tion. In patients with pericarditis, the ECG on presentation occurs in a matter of days or weeks, but may not be seen in
usually demonstrates diffuse ST-segment elevation and PR- every patient. Often, the transition from stage III to stage IV
segment depression (stage I) and evolves through three sub- is relatively slow, with some patients left with some degree of
sequent phases [20]. During the evolutionary phase (stage II), T-wave inversion for an indefinite period.
all ST-junctions return to baseline more or less in phase, Although some 80% of patients with pericarditis exhibit
with little change in T-waves. (By contrast, in patients with a typical stage I ECG during their course [21], atypical vari-
ST-segment elevation due to acute myocardial injury, T-wave ants (or even a normal ECG) may also be seen. An important
inversion begins to occur before the ST-segments return to base- ECG variant that can be quasidiagnostic is PR-segment (not
line.) The T-waves subsequently flatten and invert (stage III) in PR-interval) depression in the absence of true ST-segment el-
all or most of the leads that showed ST-segment elevations. evation, which though nonspecific, may be the only sign of
In stage IV, the T-waves return to their prepericarditic condi- pericarditis. This may occur as a consequence of superficial my-
tion. The widespread T-wave inversions that appear in stage III ocarditis affecting the atrium [22]. Although the ST-changes of
are indistinguishable from those of diffuse myocardial injury, pericarditis may occasionally resemble those of normal early
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350 Section III: Cardiovascular Problems and Coronary Care

FIGURE 35.2. Electrocardiogram (ECG) in acute pericarditis. Note the diffuse, upward concave ST-
segment elevation and PR-segment depression (lead II).

repolarization, a useful differentiating feature may be the ratio suggest an etiology, and to exclude cardiomegaly, which sug-
between the height of the ST-segment and the T-wave in lead V6 . gests the presence of a substantial pericardial effusion (>250
A ratio exceeding 0.24 favors the diagnosis of pericarditis [23]. mL). Pericardial calcification is rarely seen, but may sug-
gest constrictive pericarditis. Any suspicion for cardiomegaly
Imaging and Additional Laboratory Testing should prompt a transthoracic echocardiogram to assess for
hemodynamically significant pericardial effusion or tampon-
Although laboratory findings in patients with suspected peri- ade. Routine echocardiography in patients with unequivocal
carditis are nonspecific, measurement of serum markers of in- evidence of pericarditis and normal hemodynamics by physi-
flammation (leukocyte count, erythrocyte sedimentation rate, cal examination is probably unnecessary, though the detection
C-reactive protein, and lactate dehydrogenase) and myocardial of a pericardial effusion may help to support the diagnosis. In
necrosis (creatine kinase, and troponins) may help to estab- addition, detection of wall motion abnormalities or left ven-
lish or confirm the diagnosis, define the extent of associated tricular dysfunction on echocardiography may be helpful in
myocardial injury, and guide subsequent follow-up. The 2004 detecting associated myocardial infarction or in assessing the
European Society of Cardiology guidelines on the management severity of associated myocarditis.
of pericardial diseases [24] therefore advise measurement of
these parameters as part of the initial diagnostic evaluation in
all patients, but this recommendation remains somewhat con-
Natural History and Management
troversial. A markedly elevated white blood cell count, par- There are no large, randomized, controlled clinical trials to
ticularly in association with high fever, should raise suspicion guide the therapy of patients with acute pericarditis. Initial
for purulent pericarditis, and may prompt sampling of pericar- management is directed at screening for specific etiologies and
dial fluid (if present) for diagnosis. Cardiac enzymes including underlying conditions that may alter the treatment strategy
creatine kinase (creatine kinase, total and MB-fraction) and (e.g., connective tissue disease, HIV infection, and tuberculosis)
troponins are commonly elevated in patients with pericarditis and control of symptoms. In the vast majority of patients, acute
due to associated epicardial inflammation or myocarditis [25]. idiopathic pericarditis is a self-limited disease without signifi-
Elevations in troponin I are seen more commonly than those cant complications or recurrence, and may be safely managed
in CK-MB and are frequently associated with male gender, ST- in the outpatient setting [28]. A subset of patients with high-
segment elevation, younger age at presentation, and pericardial risk features including fever greater than 38 C, subacute course
effusion. The degree of troponin elevation is roughly related (symptoms developing over days or weeks), large pericardial ef-
to the extent of myocardial inflammation and, distinct from fusion (>20 mm in width in diastole by echocardiography), car-
acute coronary syndromes, does not appear to correlate with diac tamponade, or failure to respond to treatment with aspirin
long-term prognosis [26]. Routine measurement of cardiac tro- or nonsteroidal anti-inflammatory drugs (NSAIDs) should be
ponins in patients with suspected or definite pericarditis may considered for hospital admission to permit additional obser-
therefore be unnecessary, unless there is suspicion for asso- vation and a more extensive etiologic work-up [29]. Immuno-
ciated transmural myocardial infarction by ECG (due to the suppressed patients and those with blunt or penetrating chest
presence of pathologic Q-waves) [27]. Similarly, routine sero- trauma, serologic evidence of myocarditis (based on elevated
logic testing for antinuclear antibodies or rheumatoid factor cardiac biomarkers), or need for oral anticoagulant therapy
is rarely helpful, save in those patients in whom other clinical may also be at risk for complications and warrant closer ob-
features suggest underlying connective tissue illness. servation [30].
The chest radiograph is typically normal in acute pericardi- Treatment of pericarditis may vary on the basis of etiology.
tis, but is often performed as a matter of course to assess for For the minority of cases in which a specific diagnosis is iden-
abnormalities in the mediastinum or lung fields, which may tified, therapy should be tailored appropriately, as outlined in
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Chapter 35: Critical Care of Pericardial Disease 351

Table 35.1. (Details of treatment for specific conditions are be- munosuppression with corticosteroids, azathioprine, or even
yond the scope of this discussion.) In uncomplicated cases of id- cyclophosphamide, though there is limited clinical experience
iopathic pericarditis, treatment with NSAIDs is the cornerstone with many of these agents [38]. Caution should be exercised in
of therapy. Across the board, these agents are effective in re- particular with initiation of steroid therapy, given that many
ducing inflammation and symptoms of pain, fever, and malaise patients experience extreme difficulty in weaning once they
associated with pericarditis. Limited observational data sug- are begun. Importantly, in both the CORE and COPE trials,
gest that the various available NSAIDs have comparable ef- prednisone therapy was a strong predictor of pericarditis re-
ficacy [31]. As a first-line agent, many favor treatment with lapse, confirming the empiric observation that glucocorticoid
ibuprofen, which is well tolerated and can easily be titrated therapy is a major factor in recurrence [39]. Steroid therapy
over a range of doses. The typical dose is 600 mg every 6 hours, should therefore be reserved as a therapy of last resort for non-
which sometimes relieves pain within 15 minutes to 2 hours of tuberculous, nonconnective tissue diseaserelated pericarditis.
the first dose. Depending on patient tolerance and therapeu- When necessary, steroids should be utilized in the lowest ef-
tic response, the individual dose can be reduced to 400 mg or fective dose and rapidly weaned. Intrapericardial instillation
raised to 800 mg or greater with continued observation for side of steroids may be an alternative in refractory cases and may
effects. Should this fail, aspirin 600 to 900 mg four times per help to avert some of the side effects of systemic therapy [40].
day may be given. Indomethacin may be used, always given on Of note, pericardiectomy has occasionally been employed for
a full stomach and in divided doses from 100 to 200 mg per recurrent pericarditis, but appears to be effective in the mi-
day, beginning with 25 mg every 6 hours. In patients with my- nority of patients, perhaps because complete removal of the
ocardial infarctionrelated pericarditis, indomethacin should pericardium is not possible, and residual pericardial or pleural
probably be avoided in light of experimental work showing surfaces may remain inflamed [41].
that it reduces coronary flow, increases experimental infarction
size, and raises blood pressure. Aspirin is the agent of choice
in these cases because among the NSAIDs, it least retards scar Pericardial Effusion and Tamponade
formation in the infracted heart [32]. In all patients receiving
high-dose NSAIDs, gastrointestinal protection with an antacid Pericardial effusion may appear as a complication of acute peri-
or protonpump inhibitor should be considered to reduce the carditis or as an isolated entity. In 60% of cases, the etiology
risk of drug-induced gastritis or bleeding. is related to a known systemic disease [42]. Effusions are com-
Pain is typically relieved within hours to days of initiation of mon following cardiac surgery; as many as 10% may progress
anti-inflammatory medications. Occasionally, chest pain per- to late tamponade [43]. Severe circulatory congestion due to
sists beyond 2 weeks of therapy with an NSAID, but re- heart failure may result in transudative effusion as a conse-
sponds to therapy with a different NSAID or to the addition quence of markedly elevated intracardiac filling pressures or
of colchicine 0.6 mg twice daily. Recurrent pericarditis may obstructed pericardial drainage. Hemopericardium is a poten-
complicate 15% to 32% of cases, and can be a particularly tially lethal complication of chest wall trauma, myocardial rup-
troublesome problem [33]. Colchicine has long been known to ture, or proximal aortic dissection. In some cases of pericar-
be effective in preventing relapses of polyserositis in familial dial effusion, despite a thorough diagnostic evaluation, there
Mediterranean fever [34]. A wealth of observational data now may be no identifiable cause even when the effusion has been
support the notion that colchicine as an adjunct to therapy present for years; such idiopathic effusions generally have be-
with NSAIDs or corticosteroids is well tolerated and effective nign course, though tamponade can develop without warning
in the treatment and prevention of relapsing pericarditis [35]. over time [44]. Because of the high prevalence of idiopathic
A small, randomized, controlled trial seems to confirm this im- pericarditis, this disorder accounts for the bulk of pericardial
pression. In the Colchicine for Recurrent Pericarditis (CORE) tamponade; as noted, however, this condition typically has a
[36] trial, 84 patients with a first episode of recurrent peri- benign, uncomplicated course. By contrast, effusions associ-
carditis were randomized to conventional therapy with aspirin ated with bacterial, fungal, and HIV infection, those associ-
alone or conventional treatment plus colchicine (1.0 to 2.0 mg ated with neoplasia, and those associated with bleeding into
the first day and then 0.5 to 1.0 mg day for 6 months). Treat- the pericardial space have a high likelihood of progressing to
ment with colchicine significantly decreased the recurrence rate tamponade [45].
at 18 months from 50.6% to 24.0% ( p = 0.02, 95% confi- Pericardial effusions may have a spectrum of hemodynamic
dence interval 2.5 to 7.1) and simultaneously reduced symptom effects ranging from the inconsequential to complete circula-
persistence at 72 hours. tory collapse. As noted previously, the pericardium has a lim-
Efficacy in recurrent pericarditis has spurred interest in the ited reserve volume such that the rapid accumulation of even
utilization of colchicine in the first episode of acute pericarditis modest amounts of pericardial fluid may have important hemo-
for the prevention of recurrent pericarditis. In the Colchicine dynamic consequences for ventricular filling and overall car-
for Acute Pericarditis (COPE) [37] trial, 120 patients experi- diac performance. Slowly accumulating effusions may be ac-
encing their first episode of acute pericarditis (idiopathic, vi- commodated by pericardial stretch over time and may therefore
ral, postpericardiotomy, and connective tissue disease related) escape clinical diagnosis until they are quite large. Although
were randomly assigned to conventional treatment with as- computed tomography (CT) and magnetic resonance imaging
pirin or conventional treatment plus colchicine (1.0 to 2.0 mg (MRI) may be more sensitive for the identification of small
for the first day and then 0.5 to 1.0 mg per day for 3 months). amounts of pericardial fluid, echocardiography is the primary
Corticosteroid therapy was permitted but restricted to patients modality for evaluation of the functional consequences of any
with aspirin contraindications or intolerance. During the 2,873 pericardial effusion.
patient-months of follow-up, colchicine significantly reduced
both the symptom persistence at 72 hours and the recurrence
rate relative to conventional therapy alone (recurrence rates Cardiac Tamponade
10.7% vs. 32.3%, respectively, at 18 months, p = 0.004). Over-
all, the COPE trial provides evidence to support the use of Cardiac tamponade is defined as hemodynamically significant
colchicine as an adjunct to NSAIDs during a first episode of cardiac compression due to accumulating pericardial contents
pericarditis to prevent recurrence, though routine use of this that evoke and defeat compensatory mechanisms, resulting
agent for this indication is not recommended. in a decline in cardiac output (Fig. 35.3) [46]. The severity
Intractably symptomatic pericarditis occasionally calls for of cardiac compression may vary widely depending on the
adjunctive treatment with narcotics or more aggressive im- quantity and rate of accumulation of fluid, blood, pus, or gas
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352 Section III: Cardiovascular Problems and Coronary Care

Intrapericardial pressure

Ventricular volume

FIGURE 35.3. Cardiac tamponade


Ventricular filling Stroke volume (heavy arrows without tails) and
Blood volume Ventricular end-systolic volume
compensatory mechanisms (arrows
with tails). Thin-tailed arrows represent
Systemic and pulmonary venous pressure Atrial pressure Ejection fraction
Cardiac output
immediate mechanisms directed against
tamponade changes; intermediate
Tachycardia Inotropic effect mechanisms are represented by heavier-
Atrial pressure tailed arrows. For example, decreased
ventricular filling due to decreased
ventricular volume is immediately
Pheripheral resistance supported by increased blood volume.
Development of the latter is stimu-
lated by the intermediate mechanism,
Adrenergic stimulation increased venous pressures (see text).

(including air) in the pericardial space. Occasionally, pericar- Presentation and Diagnosis
dial effusion and tamponade are seen in combination with
Cardiac tamponade may appear insidiously as the first sign
underlying constrictive physiology (constrictiveeffusive peri-
of pericardial injury or intrapericardial bleeding, especially in
carditis). Tamponade should be considered in the differential
conditions such as neoplasia, trauma, and connective tissue dis-
diagnosis of any patient with cardiogenic shock and systemic
orders. Commonly, however, it follows clinical acute pericardi-
congestion.
tis. The symptoms of tamponade are not specific, and may be
similar to those of congestive heart failure (though frank pul-
Physiology monary edema is uncommon). Dyspnea and fatigue are com-
Understanding the physiology of cardiac tamponade is essential mon presenting complaints, and patients may have other signs
to diagnosis and treatment. The primary hemodynamic abnor- and symptoms of an associated systemic illness (e.g., malig-
mality is an increase in pericardial pressure that affects the fill- nancy or connective tissue disease). Those with advanced car-
ing of one or more cardiac chambers; due to lower filling pres- diac compression may exhibit signs of hypoperfusion, includ-
sures in systole and diastole, right-heart performance is initially ing pallor, cyanosis, confusion, diaphoresis, diminished urine
affected disproportionately to that of the left heart. For sig- output, and cold extremities. In patients with rapid tamponade
nificant cardiac compression, the pericardial contents must in- due to hemorrhage, as in wounds and cardiac or aortic rupture,
crease at a rate exceeding the rate of stretch of the parietal peri- the dominant picture is one of shock, which if unchecked, can
cardium (see Fig. 35.1) and, to some degree, the rate at which rapidly lead to electromechanical dissociation and death.
venous blood volume expands to maintain the small filling gra- On physical examination, tachycardia and hypotension (rel-
dient to the right heart. As the chambers become progressively ative or absolute) are the rule, though bradycardia may oc-
smaller and myocardial diastolic compliance is reduced, car- casionally be seen in association with myxedema or uremia.
diac inflow becomes limited, ultimately equalizing mean dias- Jugular venous distension is usually apparent, except in cases of
tolic pericardial and chamber pressures. Relentlessly increasing rapid tamponade (e.g., acute hemopericardium), in which there
intrapericardial pressure progressively reduces ventricular vol- has been insufficient time for the blood volume to increase.
ume to the point that even a high ejection fraction cannot avert The venous contour typically exhibits an absent y descent due
critical reduction of stroke volume at any heart rate. to loss of the gradient for passive ventricular filling in early di-
True filling pressure in the heart chambers is defined by the astole. The normal inspiratory fall in venous pressures is pre-
transmural pressure, which is equal to the difference between served in uncomplicated cardiac tamponade; a rise (or absence
cavity pressure and pericardial pressure. Pericardial pressure of fall) in the jugular venous pressure (Kussmauls sign) is sug-
is normally negative, and therefore augments transmural pres- gestive of associated constrictive physiology. When tamponade
sure (suction effect), facilitating cardiac filling. Increasing peri- is due to inflammatory or neoplastic lesions, pericardial rubs
cardial pressure due to accumulation of pericardial contents frequently are present and can be quite loud, although the heart
reduces and ultimately offsets transmural pressures, thereby sounds may be distant due to insulating effects of the pericar-
compromising filling. In tamponade, both the ventricles fill dial fluid and reduced ventricular function.
against a common stiffness (pericardium plus fluid), evoking Excessive fluid in the pericardium often exaggerates the nor-
corresponding increases in left and right atrial pressures. Peri- mal pericardial effects on ventricular interaction, heightening
cardial pressure quickly exceeds early diastolic pressure in the the normal inspiratory decrease in systemic blood pressure,
atria and right ventricle and rises further during ventricular leading to pulsus paradoxus. This is conventionally defined as
diastolic expansion, causing early diastolic right ventricular a drop in systolic pressure of more than 10 mm Hg with normal
collapse, which further impedes atrial emptying. Ultimately, inspiration, and may be palpable in muscular arteries (such as
there is elevation and near-complete equalization of pericardial the femoral artery) [47]. The phenomenon occurs because in
and four-chamber pressures in diastole, abolishing the normal tamponade, increased right heart filling with inspiration can
pressure gradient for filling; the ventricles may fill only during only be accommodated by bulging the atrial and ventricular
atrial systole, particularly at rapid heart rates. Because of re- septa toward the left atrium and ventricle (due to restraint by
duced filling, ventricular systolic pressure ultimately falls, along pericardial fluid). The decrease in left ventricular filling due to
with stroke volume, reducing cardiac output. As in heart fail- septal shift (enhanced by the normal decrease in left atrial fill-
ure, this fall in output triggers a cascade of compensatory neu- ing on inspiration) diminishes left ventricular stroke volume
rohormonal mechanisms that generate tachycardia, increased and arterial pressure. Although pulsus paradoxus is the hall-
contractility, enhanced circulating blood volume, and increased mark of tamponade, it may also be present in patients with
systemic vascular resistance in an attempt to defend end-organ obstructive lung disease (including severe asthma), pulmonary
perfusion (Fig. 35.3). embolism, tense ascites, obesity, right heart failure due to mitral
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Chapter 35: Critical Care of Pericardial Disease 353

stenosis or right ventricular infarction, and hypovolemic and diastolic pressure on inspiration that diminish the pressure gra-
cardiogenic shock. Because pulsus paradoxus occurs when res- dient for left ventricular filling. As a result, mitral valve opening
piratory changes alternately favor right and left heart filling, is delayed, isovolumic relaxation time is prolonged, and peak
it may be absent in conditions that balance or blunt the ef- transmitral filling velocity decreases. Reciprocal changes occur
fects of inspiratory venous return on ventricular filling (e.g., on the right side of the heart, with a resultant inspiratory in-
pericardial adhesions, atrial septal defect, severe aortic insuffi- crease in peak transtricuspid filling velocity [52]. Correspond-
ciency, or diminished left ventricular compliance due to severe ing changes are visible on Doppler interrogation of the pul-
hypertrophy, infiltrative myopathy, myocardial infarction, or monary and hepatic venous flows and may enhance the sensi-
advanced heart failure) or in cases of severe hypotension where tivity and specificity of echocardiography for diagnosis of tam-
respiratory blood pressure variations may be imperceptible. ponade [53].
Cardiac catheterization in patients with tamponade is of-
ten performed as a prelude to pericardiocentesis, but can also
Additional Diagnostic Testing be diagnostic. Typically, the hemodynamics at catheterization
The ECG in tamponade is rarely diagnostic. Clinical signs of are notable for elevation and equalization of average diastolic
pericarditis (ST-segment elevations and PR-depressions) may pressures across all four cardiac chambers in the range of 15
persist, and frequently, there is some decrease in voltage of the to 30 mm Hg. As with the jugular venous waveform, the right
QRS and T-waves (typically sparing the P-wave), reflecting in- atrial pressure tracing displays an absent y descent and pre-
sulation of the heart by surrounding fluid and the effects of served x descent, corresponding to diminished atrial emptying
cardiac compression [48]. Although common, however, low during ventricular diastole as a consequence of elevated end-
voltage is not a sensitive or specific finding for tamponade. By diastolic pressures. As with echocardiography, discordant in-
contrast, electric alternation (beat-to-beat variation in P- or spiratory changes in right- and left-sided pressures are often
QRS amplitude reflecting a shifting electrical axis as the heart seen, with a fall in left-sided filling pressures and stroke vol-
swings within a large effusion) is fairly specific for tampon- ume with inspiration corresponding to the pulsus paradoxus
ade and virtually pathognomonic when it affects the both the noted on physical examination and the diminished transmitral
P-waves and the QRS complex (simultaneous alternation) [49]. flow seen by Doppler. For reasons that remain unclear, despite
Although an enlarged cardiac silhouette on chest radiography comparable filling pressures to patients with advanced heart
may suggest a pericardial effusion, the chest radiograph alone is failure, patients with cardiac tamponade do not typically de-
rarely diagnostic because cardiomegaly, large pericardial cysts, velop pulmonary edema [54].
and pericardial effusions may be difficult to distinguish.
Echocardiography has a high degree of sensitivity and speci- Special Cases
ficity for recognizing pericardial fluid and is the key diagnostic
Because tamponade physiology is merely the result of a pericar-
test for assessing the hemodynamic significance of a pericar-
dial pressure that exceeds intracavitary pressure, it may occur
dial collection. CT, spin-echo, and cine MRI can also be used
at lower diastolic pressures (6 to 12 mm Hg) in patients who
to assess the size and extent of simple and complex pericardial
have a decrease in circulating blood volume and cardiac filling
effusions (and indeed may be more sensitive for small amounts
pressures due to hypovolemia or hemorrhage. In these condi-
of pericardial fluid), but measurements by CT and MRI tend to
tions, even a relatively modest elevation in pericardial pres-
be larger than those by echocardiography, and neither radio-
sure may lower the transmural filling pressure sufficiently to
graphic technique is typically useful in the acute management of
compromise stroke volume. Such low-pressure tamponade
patients with suspected tamponade [50]. By echocardiography,
may lack the typical hemodynamic or clinical signature, and is
a pericardial effusion typically appears as a lucent separation
typically observed in patients with preexisting effusions who
between visceral and parietal pericardium in the region of the
undergo aggressive diuresis or hemodialysis [55]. In addition,
posterior left ventricular wall. With larger effusions, the fluid
regional tamponade, affecting only limited portions of the heart
is also demonstrated anterior to the right ventricle. As pericar-
(or even a single cardiac chamber), may occur in the setting of
dial effusion increases, movement of the parietal pericardium
pericardial adhesions and loculated fluid collections, as can be
decreases. When the amount of pericardial effusion is massive,
seen after cardiac bypass surgery (even after the pericardium is
the heart may have a swinging motion in the pericardial cav-
left open). In this case, the typical hemodynamic features may
ity, the echocardiographic correlate of electrical alternans seen
not be present on conventional imaging, and diagnosis may
on the ECG.
require transesophageal echocardiography [56].
Several echocardiographic findings indicate that a pericar-
dial effusion is large enough to cause hemodynamic compro-
mise (tamponade physiology). Early diastolic collapse of the
Management
right ventricle and late diastolic right atrial inversion are seen Although pericardial effusions that are small or resolve rapidly
when pericardial pressure transiently exceeds the intracavitary with anti-inflammatory treatment may not require invasive
pressure and are characteristic, though not entirely specific therapy, those associated with hemodynamic compromise
signs of tamponade [51]. The inferior vena cava is typically should be promptly drained using either a percutaneous or
dilated with blunted respiratory variation indicating elevated surgical approach. Transient medical stabilization of patients
right-sided filling pressures. Inspiratory shift of the ventricular with tamponade physiology can often be achieved through ag-
septum toward the left and respiratory variation in ventricular gressive volume resuscitation (particularly in volume-depleted
chamber size may also be seen, reflecting right ventricular filling patients) and pressor support with inotropic agents (e.g., nore-
at the expense of the left due to essentially fixed intrapericar- pinephrine, isoproterenol, and dobutamine), but medical ther-
dial volume. Corresponding changes can be seen on Doppler apy alone is usually insufficient. Positive-pressure ventilation
echocardiography, which permits the detection of exaggerated may precipitate hemodynamic collapse due to excessive preload
respiratory variation in transmitral and transtricuspid flow reduction, and should be avoided where possible until peri-
velocities during diastole. During inspiration, intrapericardial cardial drainage can be accomplished. Percutaneous needle
pressure (and therefore left ventricular end-diastolic pressure) pericardiocentesis may be performed by trained personnel
and intrathoracic pressure normally fall to the same degree, in the cardiac catheterization laboratory or at the bedside
whereas in tamponade, intrapericardial pressure falls substan- with echocardiographic (or CT) guidance. Echocardiography
tially less than intrathoracic pressure. This leads to discordant is helpful in demonstrating the most accessible window for
changes in pulmonary venous pressure and left ventricular end- passage of a needle; typically, the subxiphoid approach is most
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354 Section III: Cardiovascular Problems and Coronary Care

effective, with insertion of a long needle underneath the xiphoid


process at a 30-degree angle to the skin, directed gradually to- Constrictive Pericarditis
ward the left shoulder until pericardial fluid is aspirated. At-
tachment of an electrocardiographic lead to the needle may Constrictive pericarditis is a rare, but severely disabling, con-
be useful for additional guidance in identifying the pericardial sequence of chronic pericardial inflammation characterized by
space because contact of the needle with myocardium generates progressive fibrosis and dense adhesion of the pericardium that
an electrocardiographic current of injury. An apical approach progressively impairs ventricular filling. Any patient with acute
(using a shorter needle inserted in the sixth or seventh rib space pericarditis may ultimately go on to develop constriction, but
in the anterior axillary line) can also be considered if adequate the syndrome appears particularly common in patients with
fluid is visible in this region by echocardiography. pericardial disease due to tuberculosis, therapeutic chest irradi-
Once the pericardial space is reached, a soft-tipped ation, prior cardiac surgery, chest trauma, or uremia. The time
guidewire is passed into the pericardial space and the nee- course of development is variable, with constrictive physiology
dle removed. A multiholed catheter can then be introduced occasionally apparent acutely (constrictiveeffusive pericardi-
over the wire, sutured in place, and connected to a reservoir tis) but more commonly seen months to years following the
to allow complete drainage of the remaining pericardial fluid initial inflammatory insult. The clinical presentation is that of
over the next several hours. Rapid reduction in intrapericardial marked venous congestion in the face of relatively preserved
pressures and associated hemodynamic improvement may be cardiac size and systolic function, and resembles that of right
seen after the aspiration of only 100 to 200 mL of fluid. Fluid heart failure. Patients typically experience dyspnea, easy fati-
specimens should be sent for appropriate chemistry, cytology, gability, and abdominal distension, and may exhibit dramatic
and culture as appropriate for more definitive identification of physical findings including ascites, peripheral edema, and jugu-
etiology and direction of appropriate adjuvant therapy. lar venous distension with prominent x and y descents. The dif-
For patients with intrapericardial hemorrhage (e.g., due to ferential diagnosis is broad, and commonly includes restrictive
proximal aortic dissection) or tamponade due to purulent peri- cardiomyopathy, hepatic cirrhosis, or right heart failure due
carditis, surgical drainage may be optimal. A surgical approach to any of a variety of causes including pulmonary embolism,
may also be necessary in patients with rapid reaccumulation right ventricular infarction, venous/valvular obstruction, or cor
of pericardial fluid following pericardiocentesis (as is common pulmonale.
in patients with malignant effusions), patients with loculated
effusions causing regional tamponade (as following cardiac Pathophysiology and Diagnosis
surgery), or in patients with large intrapericardial clots that are The fundamental physiologic abnormality in constrictive peri-
not amenable to catheter drainage. The two most commonly carditis is limited filling and enhanced interventricular depen-
utilized surgical options are surgical subxiphoid incision and dence because of rigid encasement of the heart by thickened
drainage and video-assisted thoracoscopic drainage [57] with pericardium. Because the myocardium is intrinsically normal
creation of a pleuropericardial window to allow longer term (unless there is a combined abnormality, as in patients with
egress of pericardial fluid into the pleural space. Thoracoscopic prior mediastinal irradiation), myocardial contractile function
surgery provides the opportunity for concurrent performance and relaxation may also be entirely normal (distinct from
of additional procedures such as biopsy of the lung, biopsy restrictive cardiomyopathy). Unlike cardiac tamponade, the
of pleural or mediastinal masses, or management of a con- heart is not compressed in early diastole and relaxes rapidly as
comitant pleural effusion, but requires single-lung ventilation filling proceeds until it reaches its pericardial limit (rubber-bulb
and lateral decubitus positioning, which may preclude use of effect). Early diastolic filling is rapid due to elevated right atrial
this approach in an emergency. Both the approaches may be pressures, but abruptly limited by the noncompliant pericardial
accomplished with limited perioperative morbidity, and con- shell, generating the classic dip and plateau or square root
version to an open surgical approach (median sternotomy or contour on intraventricular pressure recordings in diastole (Fig.
anterolateral thoracotomy) is rarely necessary [58]. In patients 35.4). As the heart is effectively isolated from intrathoracic
who are poor candidates for surgical drainage, percutaneous pressure variations by the stiff pericardial shell, jugular ve-
balloon pericardiotomy may be an effective alternative [59]. nous pressure increases during inspiration (Kussmauls sign)

A B

FIGURE 35.4. A: Right atrial pressure recording in a patient with constrictive pericarditis. Note the steep
x and y descents, corresponding to the changes visible in the jugular venous contour. B: Simultaneous
recording of LV (yellow) and RV (green) (pressure in the same patient). Note the near equalization of
LV/RV pressures in diastole and the square root or dip and plateau sign reflecting abrupt cessation
of ventricular filling due to pericardial constraint.
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Chapter 35: Critical Care of Pericardial Disease 355

and pulsus paradoxus is typically absent, except in cases associ- vena cava as well as pericardial thickening. Any thickening
ated with pericardial fluid under pressure (constrictiveeffusive greater than 3.5 mm (and more definitively >6 mm) is sug-
pericarditis). gestive and helps to differentiate constrictive from restrictive
Like tamponade, constriction is characterized by elevation cardiomyopathy. Although increased pericardial thickness has
and equalization of left- and right-heart filling pressures, but been considered an essential diagnostic feature of constrictive
there are important clinical differences. Distinct from tampon- pericarditis, it should be remembered that in a large surgical
ade, venous pressure contours show prominent y as well as series from the Mayo Clinic constriction was present in 18%
x troughs. The y descent also tends to be deeper and more of the patients with normal pericardial thickness [61]. In ad-
precipitous in constriction, as there is torrential filling in early dition, constrictive pericarditis may rarely develop only in the
diastole, with abrupt cessation of filling on reaching the pericar- epicardial layer in patients with previously removed parietal
dial limit. At this point, there may be an intense early diastolic pericardium [62].
third heart sound (sometimes called a knock). Clinical signs The most difficult pathophysiologic differential is typically
of right heart failure (due to elevated diastolic pressures) tend between restrictive cardiomyopathy (due to primary myocar-
to dominate those of left heart failure, perhaps because cardiac dial disease such as amyloidosis or hemochromatosis) and con-
output is relatively well preserved, and neurohormonal stim- strictive pericarditis (see Table 35.2). Historical features often
uli for salt and water retention may accordingly be less than provide clues to systemic illness that suggest a diagnosis, but
that in systolic heart failure. The precordium is usually quiet additional hemodynamic evaluation is often necessary. Typi-
to palpation, with no easily identifiable point of maximal im- cally, patients with restrictive cardiomyopathies tend to have
pulse and the liver is often palpable and pulsatile. Laboratory higher left- than right-sided pressures and show greater in-
findings are rarely diagnostic and are typically those of hepatic equalities during exercise and slower early- to midsystolic fill-
congestion and synthetic dysfunction. Hypoalbuminemia may ing. Doppler echocardiography with tissue Doppler imaging or
occur as a consequence of liver impairment, malnutrition due color M-mode imaging may be particularly helpful for distinc-
to protein-losing enteropathy, or a proteinuric nephrotic syn- tion, showing marked respiratory variation in the peak early
drome, related to chronically high venous pressures [60]. ECG mitral inflow velocity (peak E-variation 25%), rapid mitral
and chest radiograph findings are entirely nonspecific, though annular relaxation velocity (Ea 8 cm per second), and a slope
pericardial calcification may occasionally be seen (particularly of more than or equal to 100 cm per second for the first aliasing
in patients with tuberculous pericarditis). contour in the flow propagation velocity in patients with pri-
Imaging with CT or MRI may support the diagnosis of con- mary constrictive rather than restrictive disease [63,64]. Car-
striction, and typically demonstrates tube-like ventricles, atrial diac catheterization has traditionally been the gold standard
enlargement, septal changes, and enlargement of the inferior for differentiation, though hemodynamic profiles may overlap

TA B L E 3 5 . 2
DIFFERENTIATION OF CONSTRICTIVE PERICARDITIS AND RESTRICTIVE CARDIOMYOPATHY

Feature Constrictive pericarditis Restrictive cardiomyopathy

Prominent y descent in venous pressure Present Variable


Pulsus paradoxus 1/3 of cases Absent
Pericardial knock Present Absent
Cardiac catheterization
Equalization of right/left heart filling Present Left typically 35 mm Hg higher than
pressures right
Filling pressures >25 mm Hg Rare Common
Pulmonary artery systolic pressure Rare Common
>60 mm Hg
Square root sign on RV/LV diastolic Present Present
pressure waveform
Respiratory variation in leftright Exaggerated Normal
pressures/flows
Echocardiography
Ventricular wall thickness Normal Typically increased
Atrial size Possible left atrial enlargement Biatrial enlargement
Septal bounce Present Absent
Inspiratory variation in peak mitral inflow Typically >25% Typically varies by <10%
velocity (E)
Blunting of pulmonary venous systolic flow Absent Present
(S-wave on PV Doppler)
Mitral annular relaxation velocity on Typically normal or mildly reduced Diminished
Doppler tissue imaging
Slope of flow propagation velocity on color Increased, >100 cm/s Diminished
M-mode
Other
Pericardial thickness (CT/MRI/TEE) Increased Normal
Endomyocardial biopsy Usually normal or only mildly abnormal May reveal infiltrative cardiomyopathy
or extensive fibrosis, but may be
normal
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356 Section III: Cardiovascular Problems and Coronary Care

TA B L E 3 5 . 3
EVIDENCED-BASED MANAGEMENT OF PERICARDIAL DISEASE

Limited evidence from randomized trials is available to guide therapy of patients with peri-
cardial disease
The addition of colchicine to conventional medical therapy reduces the recurrence rate in
patients presenting with recurrent pericarditis [36]
The addition of colchicine to conventional medical therapy may also be useful in reducing
the duration of symptoms and the recurrence rate in patients with a first episode of acute
pericarditis [37]
Treatment with nonsteroidal anti-inflammatory drugs is not useful in the management of
persistent pericardial effusion following cardiac surgery [43]
Two-dimensional echocardiography is preferable to CT or MRI for the initial evaluation of
patients with pericardial effusion or suspected tamponade [50]
In large observational studies of patients with constrictive pericarditis, older age, prior medi-
astinal radiation, and advanced heart failure predict poor outcomes following pericardiectomy
[62,63]

considerably in the two states. Simultaneous left and right heart age slightly inferior to that of age- and gender-matched controls
pressure recordings reveal equalization and elevation of pres- (57% 8% at 10 years). In the reported Mayo Clinic experi-
sures in the right atrium, right ventricle, left atrium pulmonary ence, older age at presentation, poor preoperative New York
capillary wedge pressure (PCWP), and left ventricle during di- Heart Association functional class, and prior radiation were
astole. The right atrial (RA) pressure contour typically shows the strongest predictors of early mortality [68]. A second series
an M- or W-configuration with prominent x and y de- of 163 patients undergoing pericardiectomy over a 24-year pe-
scents (Fig. 35.4). Systolic right ventricular pressure rises, but riod at the Cleveland Clinic suggested that in addition to age
usually to less than 50 mm Hg, and the right ventricular end- and prior radiation, poor renal function, elevated pulmonary
diastolic pressure to systolic pressure ratio is usually greater artery systolic pressure, low serum sodium, and preoperative
than 0.3. Pulmonary hypertension is not a feature of constric- left ventricular (LV) dysfunction were important correlates of
tive pericarditis and indicates coexisting cardiac or pulmonary poor overall survival [69]. Seven-year survival in this experi-
disease. Discordance or separation between right ventricular ence ranged from 88% for patients with idiopathic constrictive
and left ventricular pressure contours with quiet inspiration or pericarditis to 27% for patients with postradiation constrictive
following fluid challenge is a marker of enhanced interventric- pericarditis, suggesting that the outcome of pericardiectomy is
ular interdependence and is a highly specific marker of con- highly dependent on the specific cause, the degree of preoper-
striction [65]. Endomyocardial biopsy may also be useful in ative myocardial injury, and preoperative functional capacity.
identifying primary myocardial disease when less invasive di- Early diagnosis and therapy are important because the antici-
agnostic modalities are inconclusive or ambiguous [66]. pated postoperative outcome is heavily affected by preopera-
tive heart failure severity. In addition, because pericardiectomy
Management does not affect the course of underlying myocardial disease,
careful exclusion of coincidence restrictive heart disease is im-
Medical management of constrictive pericarditis resembles that
portant in selecting patients for surgery.
of congestive heart failure because most signs and symptoms
are related to systemic congestion. Diuretics are the mainstay
of therapy and are useful in relieving volume overload and con-
gestive symptoms, but do not alter the course of the disease. CONCLUSION
Definitive treatment requires surgical pericardiectomy. Access
is typically obtained via either anterolateral thoracotomy or Pericardial manifestations are seen in a wide spectrum of in-
median sternotomy, with the target of removing as much peri- fectious, inflammatory, and neoplastic disorders. Critical care
cardium as possible (ideally, from phrenic nerve to phrenic of patients with pericardial disease depends on a basic under-
nerve). Areas of strong calcification or dense scaring may be standing of pericardial physiology and thoughtful integration
left as islands to avoid major bleeding. Pericardiectomy for of data from physical examination, electrocardiography, non-
constrictive pericarditis carries a perioperative mortality rate invasive cardiovascular imaging, and invasive hemodynamic
of roughly 6%, and normalization of cardiac hemodynamics studies. Although limited data from randomized controlled tri-
is reported in the minority of the patients, though most expe- als are available to direct the optimal strategy for treatment of
rience clinically relevant functional improvements [67]. Major patients with acute pericarditis, pericardial effusion, and peri-
complications include acute perioperative heart failure (likely cardial constriction, a wealth of observational experience pro-
due to underrecognized myocardial fibrosis or atrophy present vides important insights into the natural history and clinical
prior to surgery) and ventricular wall rupture. management of these conditions.
If an indication for surgery is established early, long-term Advances in critical care of pericardial disease, based on
survival after pericardiectomy may be good, though on aver- best available evidence, are summarized in Table 35.3.

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358 Section III: Cardiovascular Problems and Coronary Care

CHAPTER 36 ACUTE AORTIC SYNDROMES


LEON M. PTASZEK, ERIC M. ISSELBACHER AND AMY E. SPOONER

the abdominal aorta (5%) also occur [3]. Two classification


INTRODUCTION systems for dissection location are in common use (Fig. 36.1).
The DeBakey system includes three types of aortic dissection.
Representing the most lethal conditions affecting the aorta, Type I involves dissection of both the ascending and descending
acute aortic syndromes are associated with a high mortality aorta, and/or the arch. Type II dissection involves only the as-
rate if not recognized and treated promptly. Although the clas- cending aorta proximal to the brachiocephalic artery, and type
sical presentation of aortic agony is characterized by severe, III involves only the descending aorta distal to the left sub-
sudden-onset pain in the chest or back [1], this presentation, clavian artery [4]. The Stanford system includes two dissection
although quite recognizable, occurs only in a minority of cases. types. All dissections involving the ascending aorta are included
As the initial manifestations of acute aortic syndromes are fre- in type A: this includes types I and II in the DeBakey system.
quently variable, arriving at the appropriate diagnosis in a Stanford type B includes all dissections that do not involve the
timely manner may be quite challenging. Prompt recognition ascending aorta [5]. Classification of the location of a dissection
of the acute aortic syndromes may be the difference between carries prognostic and treatment importance. Surgery is indi-
life and death for the afflicted patient. Frequently, the clinician cated for dissection of the ascending aorta, whereas medical
must depend on subtle findings gleaned from history, detailed management is frequently the treatment of choice for descend-
physical examination, and imaging in order to decide on an ing dissection.
appropriate treatment plan. Here, we review the commonly en- Chronicity of the dissection is defined as the time interval
countered aortic syndromes, with a focus on aortic aneurysm between onset of symptoms and evaluation. Dissections that
rupture, as well as acute aortic dissection and acute aortic in- are present for less than 2 weeks are defined as acute, whereas
tramural hematoma (IMH). We focus primarily on the means those that are present longer are defined as chronic [6]. It is
by which these syndromes can be recognized and treated. At- noteworthy that the mortality associated with untreated as-
tention is also given to etiology and pathophysiology of the spe- cending aortic dissection reaches 75% at 2 weeks [7].
cific disease processes to the extent that evaluation of these pro- Not all cases of aortic dissection are associated with an iden-
cesses is relevant to diagnostic and treatment strategies. Because tified area of intimal tear. Several analyses have revealed that up
patients with suspected acute aortic syndromes are frequently to 13% of cases of apparent dissection turn out to be an IMH: a
critically ill and require rapid disposition to treatment, we offer hemorrhage within the media that does not communicate with
a unified evaluation and treatment algorithm. Each individual the intraluminal space [79]. In some cases, an atherosclerotic
section serves as a guide to a syndrome-specific evaluation. Key ulcer that penetrates from the intima beyond the internal elas-
features of a focused history and physical examination are em- tic lamina is thought to precipitate intramural bleeding [10].
phasized. In addition, critical laboratory and imaging tests are Classical aortic dissection and IMH are discussed separately
reviewed. later.

AORTIC DISSECTION
CLASSIC AORTIC DISSECTION
Definition and Classification
Epidemiology
Dissection of the aortic wall involves longitudinal cleavage of
the muscular media, leading to the formation of a second (or Estimates of the incidence of aortic dissection range from 2 to
false) vessel lumen. The inciting event for a typical aortic dissec- 4 per 100,000 per year [11]. The highest incidence occurs in
tion is thought to be a tear in the intima that leads to exposure patients in their sixth and seventh decades of life. Incidence
of the underlying media, presumably weakened by medial de- among men is double that for women [1,12]. Recent studies
generation. Once created, this cleavage front advances due to show that women tend to present later and with a more ad-
wall strain created by physiologic blood pressure. The cleav- vanced disease state [12]. In addition, it has been shown that
age front typically advances in the direction of blood flow, but aortic dissection exhibits diurnal and seasonal rhythms. Dissec-
dissection against the direction of flow is also observed [2]. tions are most likely to occur in the morning or early afternoon,
There are multiple consequences of dissection. The native and more commonly in winter [13]. This seasonal difference
(or true) lumen is frequently compressed, leading to compro- does not appear to depend on climate [14].
mised downstream blood flow. The false lumen of the dissected Mortality rates associated with dissection are very high, and
aorta may also be less able to withstand physiologic blood pres- many patients do not survive to hospital admission. For those
sure, due to changes in both its shape and its thinner external patients with aortic dissection who survive to admission, the
wall. The damaged aorta may therefore be more prone to rup- early mortality rate is estimated to be as high at 1% per hour
ture. during the first day [7]. If left untreated, the associated mor-
Aortic dissections are generally classified by location and tality is estimated at 50% at 7 days and greater than 90% at
extent. Dissections originate in the ascending aorta (65%) or 90 days [15]. Among patients who receive treatment, mortality
in the descending aorta just distal to the origin of the left sub- during initial hospitalization ranges between 15% and 27.5%,
clavian artery (20%). Dissection in the aortic arch (10%) and as reported in several longitudinal studies [1,16,17].
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Chapter 36: Acute Aortic Syndromes 359

Iatrogenic injury to the aortic wall, sustained in the context


of cardiac catheterization, intra-aortic balloon pump place-
ment, or cardiac surgery, increases the risk of future aortic
dissection [3032]. Cardiac surgery involving the aortic valve
appears to pose the greatest risk. Damage sustained by the aorta
may take up to several years to develop into aneurysm and/or
dissection [32,33].
Blunt trauma or rapid deceleration injury is frequently as-
sociated with injury to the aortic isthmus. Although this type
of injury may be associated with tearing or transection of the
aorta, a true dissection is uncommon [34,35].

FIGURE 36.1. Dissection classification (DeBakey/Stanford). [ c Mas-


sachusetts General Hospital Thoracic Aortic Center. Used with permis- Clinical Manifestations
sion.]
There is no single physical examination finding that allows for
positive identification of dissection: only imaging of the aorta
Etiology and Pathophysiology verifies the diagnosis. Consequently, the initial evaluation and
examination must incorporate a high index of suspicion and
Any process that causes damage to the aortic tunica media, careful assessment.
leading to medial degeneration, increases the risk for aneurysm The classic initial symptom of acute aortic dissection is se-
or dissection. In the case of typical aortic dissection, the pre- vere chest or back pain. The severity of this pain is characteris-
cipitating event is thought to be the creation of a tear in the tically at its maximum at the point of inception. This is in sharp
intimal layer overlying a damaged area of the media. In the contrast with the typical crescendo onset of myocardial infarc-
elderly patient with dissection, the presence of medial degener- tion pain [1]. The quality of the pain is often described as being
ation is correlated with the effects of aging, hypertension, and tearing or stabbing. Acute pain is present in 85% of the
atherosclerotic disease [1820]. Indeed, hypertension is found patients described in the International Registry of Aortic Dis-
in 70% to 80% of patients with aortic dissection [1]. eases (IRAD) and is present in up to 96% of patients described
In the younger patient with aortic dissection, medial de- in other studies [1,6,36]. Of the patients in the IRAD registry,
generation is still the culprit, but the constellation of corre- 90% described this discomfort as being the worst pain they
lated risk factors tends to differ [21]. Typically, young patients ever experienced. Indeed, patients may be prone to writhing
are more likely to have hereditary connective tissue disorders or pacing because of the pain. The initial location of the pain
that compromise the integrity of the extracellular matrix in is correlated to the location of the dissection: of the patients
the tunica media, most notably Marfan syndrome, Ehlers in reported clinical series who presented with anterior chest
Danlos syndrome, bicuspid aortic valve, or familial thoracic or neck pain, 65% to 90% were found to have dissection of
aortic aneurysm syndrome (FTAAS) [1,6,21]. Young patients, the ascending aorta. Interscapular or back may also represent
defined in a recent study as being 40 years of age or younger, are dissection of the descending aorta [6]. On occasion, the pa-
also less likely to be hypertensive, and may have a larger aor- tient may report a migration of the pain in association with
tic diameter on presentation. Paradoxically, mortality in this extension of the dissection. In a series reported by Spittell et
younger cohort does not appear to be lower than that in older al., 17% of patients reported pain migration [6]. Recently, it
patients [21]. All of these syndromes have been associated with was noted that aortic dissection may, in some instances, present
breakdown of the fibrillin and collagen components of the ex- with abdominal pain [37].
tracellular matrix in the media, leading to medial degeneration. A common finding at the time of presentation is hyperten-
Aortic dissection risk is also increased in patients with Turner sion. Of the patients in the IRAD series, 36% of patients with
and Noonan syndromes [6]. Increased risk for dissection is type A dissection had elevated blood pressure, whereas 70% of
found in a number of other conditions, including aortitis, espe- patients with type B dissection had hypertension. Conversely,
cially in the context of giant cell arteritis and Takayasu arteritis hypotension may also be a presenting feature of aortic dissec-
[6,22,23]. Cocaine use has also been associated with dissection, tion. This is a particularly ominous finding, as it likely repre-
ostensibly on the basis of increases in cardiac output, blood sents developing shock. Hypotension is seen more frequently
pressure, or as a consequence of direct vascular injury from in patients with type A than type B dissection (25% vs. 4%,
cocaine itself (i.e., cocaine-induced vasculitis/endarteritis). In respectively) [1]. It is also noteworthy that patients with dissec-
particular, crack cocaine has been identified as a potential tions who present with a deadly triad of hypotension/shock,
precipitant of dissection [24,25]. an absence of pain, and evidence of branch vessel involvement
As is the case for aortic aneurysm, the presence of certain exhibit a markedly higher mortality [38].
structural abnormalities may be associated with an increased Evidence of heart failure, most notably pulmonary edema
risk of dissection. In particular, a correlation has been described and hypotension, is found in up to 7% of patients with aortic
in patients with bicuspid aortic valve or, uncommonly, aortic dissection [1,6]. This finding is most frequently due to aortic
coarctation. This association does not appear to be related to regurgitation caused by a type A dissection [39]. However, in
the hemodynamic effects of the abnormalities [26]. a recent report, a surprisingly high percentage of patients with
Notably, pregnancy is an independent risk factor for aortic heart failure at the time of dissection actually had a type B
dissection. The highest incidence of dissection is observed in syndrome, with heart failure presumably due to myocardial
the third trimester or early postpartum period. This risk is high ischemia or diastolic dysfunction with hypertension.
particularly in pregnant women with a bicuspid aortic valve, Syncope is present in up to 9% of patients with dissection. In
Marfan, EhlersDanlos, or Turner syndrome [27,28]. In preg- these patients, syncope that is associated with focal neurologic
nant women with Turner syndrome, the risk of dissection or signs is usually the result of occlusion of a branch vessel. Syn-
rupture exceeds 2%, and the risk of death is increased 100-fold cope in the absence of any other neurologic findings, present
[29]. Sporadic aortic dissections may occur in women with- in up to 5% of dissection patients, likely represents aortic rup-
out these predisposing conditions, possibly due to the elevated ture into the pericardial space with tamponade. This finding
levels of relaxin and inhibin associated with pregnancy. portends rapid decline and requires emergent surgery.
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360 Section III: Cardiovascular Problems and Coronary Care

Pericardial tamponade in the context of type A aortic dissec- In most hospital settings, a chest x-ray (CXR) is performed
tion is a surgical emergency, as it represents a tenuously com- as a matter of course in the evaluation of chest pain. The CXR,
pensated rupture of the aorta. Unless the patient is in extremis, which is noninvasive, inexpensive, and routinely performed
pericardiocentesis should not be performed, as the release at the bedside, offers much useful information. In the patient
of pressure in the pericardial space may precipitate a rise in with an aortic dissection, the CXR may reveal an abnormal
blood pressure, recurrent hemorrhage into the pericardium, aortic silhouette [1,6]. Widening of the mediastinum is a vari-
and cardiovascular collapse [40]. Dissection into the pleural able finding, observed in 15% to 60% of cases. Another sug-
space may also lead to hypotension and syncope, and similarly gestive finding is separation of intimal calcium, if present, from
requires immediate surgical intervention. the soft-tissue border of the aorta. In addition, extravasation of
A number of other vascular complications of aortic dissec- blood into the pericardial space may be visualized as expanded
tion may be apparent on initial evaluation. In up to 20% of and blunted heart borders. Pleural effusions are also easily
the cases reported in the IRAD series, subjects presented with visualized on CXR. Although useful, the CXR cannot be con-
signs and symptoms consistent with occlusion of branch ves- sidered a definitive study. Therefore, other modalities should
sels. These occlusion events are typically the result of the exten- be used, notably echocardiography, computerized tomogra-
sion of the dissection into a branch vessel (static occlusion), phy (CT) scanning, and magnetic resonance imaging (MRI)
occlusion of the ostium of the vessel due to migration of the (Table 36.1).
intimal flap (dynamic occlusion), or impaired flow in the Transthoracic echocardiography (TTE) is a readily avail-
true lumen due to distention of the false lumen. The spectrum able, noninvasive, and portable imaging modality that may be
of clinical findings associated with aortic side-branch involve- considered. A focused study can be performed within 15 min-
ment ranges from no signs and symptoms, to subtle findings, to utes at the bedside. Dissected segments of aorta can be mea-
florid manifestations, including severe ischemia of the affected sured directly: this is typically restricted to the ascending aorta,
territories. The mass effect of the dissection may lead to focal as neither the aortic arch nor the descending aorta can be re-
neurologic defects in rare cases. Involvement of a subclavian liably visualized via an external approach. TTE is also a very
artery may lead to a difference in measured blood pressure reliable technique for the visualization of pericardial effusion.
between the two arms or pulse deficit. Impaired flow in the The intimal flap of aortic dissection may be seen as a dou-
mesenteric arteries leads to signs and symptoms consistent with ble aortic wall. Direction of Doppler flow may also help the
mesenteric ischemia. Dissections may also lead to occlusion of clinician distinguish between the true and false lumens of
the renal arteries, leading to acute renal failure or renal infarc- aortic dissection. It should be noted that sensitivity for type A
tion. Rarely, dissection leads to spinal artery occlusion with dissection varies between 70% and 90%, and sensitivity for
resultant paraparesis or paraplegia [1,6]. Lower limb ischemia type B dissection is approximately 40% [49]. Given this sub-
may also occur in type B dissection [41]. optimal sensitivity, performing a TTE should not delay a more
On occasion, type A dissection may extend proximally to sensitive imaging study. Despite its convenience, TTE is limited
the ostia of the coronary arteries, leading to myocardial infarc- in that it does not offer an unobstructed view of all portions of
tion. Three percent of the patients in the IRAD series presented the aorta. Body habitus may also adversely affect the quality
with dissection-related myocardial infarction, with attendant of TTE images.
chest pain and biomarker elevation [1]. A far more accurate ultrasound study for suspected aor-
There is not yet a specific biomarker in common clinical use tic dissection is transesophageal echocardiography (TEE). By
that allows the clinician to confirm the diagnosis. For example, virtue of the close proximity of the aorta to the ultrasound
the d-dimer is elevated in dissection, but has limited diagnos- probe in the esophagus, this technique offers clear views of
tic utility [42,43]. Recent work has highlighted several specific most portions of the thoracic aorta and affords excellent infor-
biomarkers that are elevated in acute aortic dissection and may mation regarding aortic valve function. TEE may be useful to
become diagnostically useful in the future. The most promis- guide surgical intervention for type A aortic dissection. TEE,
ing assay is an enzyme-linked immunosorbent assay (ELISA) like TTE, is portable and can be performed easily at the bed-
for myosin heavy chain. The sensitivity and specificity of this side, which makes it the procedure of choice for evaluation of
test, when it is performed within 12 hours of the acute event, critically ill or medically unstable patients who may be at higher
are 90% and 97%, respectively. The primary advantage of this risk during transportation for radiographic examinations.
test is its ability to distinguish dissection from other events, In aortic dissection, TEE is superior to TTE in visualization
such as myocardial infarction. Assays for other compounds el- of the intimal flap; sensitivity varies between 90% and 100%,
evated in aortic dissection but not in other acute cardiac events, and specificity is approximately 90%. Color Doppler imaging
such as serum heart-type fatty acidbinding protein, elastin, may identify the blood flow between the true and false lumens.
and calponin, are also in development [4447]. Perhaps the most important procedural drawback regarding
TEE is the need for conscious sedation, which may be difficult
to administer in a patient who is hemodynamically unstable.
CT scanning allows for a full view of the entire aorta. Con-
Imaging sequently, the sensitivity (90% to 100%) and specificity (90%)
for visualization of the intimal flap in aortic dissection are com-
Prompt imaging is critical in the evaluation of suspected aortic parable to TEE [49]. Specific CT techniques, such as spiral
dissection. Multiple modalities are at the disposal of the clin- CT, also allow for facile three-dimensional reconstruction. The
ician; however, the patient is best served by the modality that double barrel produced by dissection can be quite distinct. In
offers adequate image quality without delay or transport time. classic aortic dissection, an intimal flap can be seen, separating
The specific technique of choice may differ among hospitals, a true and false lumen. Pericardial and pleural effusions may
as not all facilities have the same capabilities. Following is a be easily visualized, but blood flow and tamponade physiology
discussion of the relative strengths and weaknesses of the com- cannot be assessed directly. A diagnostic CT scan requires in-
monly available imaging techniques in the diagnosis of aortic travenous contrast, and care must be taken to address the risks
dissection. The decision regarding the optimal technique to be of allergic reaction and contrast nephropathy. Many patients
used in a specific context is left to the individual clinician. Fre- presenting with the acute aortic syndromes may also have renal
quently, multiple imaging modalities must be used in a single insufficiency or failure; however, in the critically ill patient in
patient. In addition, a single patient may require serial studies whom aneurysm rupture is suspected, definitive diagnosis and
if his/her signs or symptoms evolve [48]. treatment of the aortic process should take priority.
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Chapter 36: Acute Aortic Syndromes 361

TA B L E 3 6 . 1
IMAGING MODALITIES FOR PATIENTS WITH SUSPECTED ACUTE AORTIC SYNDROMES

Key findings Advantages Disadvantages

TTE Intimal flap in ascending aorta Readily available Only aortic root and ascending aorta
Dilatation of aortic root Noninvasive can be reliably assessed
Aortic valve regurgitation Quickly performed at bedside Image quality may be affected by body
Pericardial effusion No ionizing radiation habitus
Color Doppler differentiation of Intravenous contrast not required Branch vessels and intramural
flow in dissection-related true Aortic valve function can be hematomas are not reliably
and false lumens directly assessed visualized
TEE Intimal flap in aorta Readily available Distal thoracic and abdominal aorta
Dilatation of aorta Noninvasive cannot be visualized
Aortic valve regurgitation Quickly performed at bedside May only be performed by trained
Pericardial effusion No ionizing radiation personnel
Color Doppler differentiation of Intravenous contrast not required Sedation required
flow in dissection-related true Image quality not affected by body Branch vessels are not reliably
and false lumens habitus visualized
Ascending aorta, arch, and
proximal descending aorta may
be visualized
Aortic valve function can be
assessed directly
CT Intimal flap in aorta Readily available Requires use of ionizing radiation and
Dilatation of aorta in any segment Noninvasive intravenous contrast
Pericardial effusion Quickly performed Transportation to scanner may be
Dissection-related true and Image quality not affected by body required in some centers
false lumens or intramural habitus Patient monitoring during scan may be
hematoma accentuated with Full aorta may be assessed in single difficult
contrast scan Aortic valve function cannot be
Most widely used first imaging test assessed directly
in suspected dissection
MRI Intimal flap in aorta Noninvasive Not readily available at many hospitals
Dilatation of aorta in any segment No ionizing radiation Transportation to scanner may be
Pericardial effusion Image quality not affected by body required in some centers
Dissection-related true and habitus Patient monitoring during scan may be
false lumens or intramural Full aorta may be assessed in single difficult
hematoma may be differentiated scan Scan time longer than other modalities
Branch vessel visualization is
excellent
Contrast not required to visualize
intramural hematoma or to
differentiate between true and
false lumen
Aortic valve function can be
directly assessed
Aortogram Intimal flap in aorta Best modality for branch vessel Invasive
Dilatation of aorta in any segment visualization Study not as readily available due to
True and false lumens may be Allows for assessment of full aorta required assembly of trained
differentiated with contrast personnel
Ionizing radiation and intravenous
contrast required
Intramural hematoma cannot be
reliably assessed

CT scanning and MRI share several of the same advan- availability: not all hospitals have MR scanners available
tages, such as high image resolution and the ability to scan for emergent use. Even when available, issues of transport-
the entire aorta. Overall, the sensitivity and specificity of inti- ing a potentially unstable patient are still present. MRI is
mal flap detection by MRI are nearly 100% [49]. MRI does also contraindicated in patients in whom vascular clips, im-
not require the use of IV contrast, which represents an ad- plantable cardioverter-defibrillators (ICDs) or pacemakers are
vantage over CT scanning; however, MRI is more expen- present.
sive and not as readily available or as rapidly performed In the past, retrograde aortography was considered the gold-
as CT scanning. The primary limitation of MRI is lack of standard technique for aortic imaging. Because aortography is
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362 Section III: Cardiovascular Problems and Coronary Care

an invasive test that requires the assembly of a catheterization of dissection. The goal heart rate is 60 beats per minute, and
laboratory team and the use of IV contrast and ionizing radi- the goal systolic blood pressure is no higher than 120 mm Hg.
ation, it is typically reserved for those cases where diagnostic In the event that a patients blood pressure is still elevated even
uncertainty remains after one or more other imaging studies after a goal heart rate has been reached with -blockade, nitro-
have been obtained. The ability of aortography to detect aortic prusside may also be administered as a constant intravenous in-
dissection depends on the presence of blood flow between the fusion; however, intravenous nitroprusside should not be used
true and false lumens; therefore, in cases where blood flow be- without concomitant -blockade, given the possibility of an
tween these chambers is limited, the aortogram may be nondi- increase in heart rate and dP/dt accompanying its potent va-
agnostic. Overall, among patients with classic aortic dissection, sodilatory effects.
the sensitivity and specificity for intimal flap visualization are In the event that a beta-blocker cannot be used, due to con-
80% to 90% and 90% to 95%, respectively [49]. Aortogra- traindications such as bronchospasm, nondihydropyridine cal-
phy is still the study of choice for visualization of aortic branch cium channel blockers are the second-line agents. Verapamil
vessels, which may not be visualized with other imaging modal- and diltiazem, both of which have vasodilator and negative
ities as well. In addition, aortography is particularly useful if inotropic/chronotropic effects, may be used. Some patients
endovascular treatment is contemplated. have hypertension that is resistant to blockade of both -
adrenergic receptors and calcium channels. In this case, dos-
ing of an intravenous angiotensin converting enzyme inhibitor,
Management such as enalaprilat, may be indicated.
Hypotension may be seen in conjunction with dissection. It
The primary goal of treatment in a patient with aortic dissec- should be noted that the mode of blood pressure measurement
tion is to minimize the effects of the dissection while rapidly should be scrutinized before changing a treatment plan; pseu-
evaluating the patients candidacy for surgical repair, if indi- dohypotension may occur if dissection propagates into the
cated (Figure 36.5). Initial medical management while waiting limb in which blood pressure is being measured. In such cases,
for possible surgery should focus on management of pain, de- it is recommended that hypotension be verified by measure-
crease of blood pressure to a minimum acceptable level, and ment of blood pressure in other limbs prior to discontinuation
decrease in the force of left ventricular contraction (dP/dt). In of beta-blockers or calcium channel blockers (Tables 36.2 and
general, long-acting agents are not favored, as such agents are 36.3).
difficult to titrate rapidly. Early observation should occur in
an intensive care setting, with an arterial line in place. For
patients presenting with evidence of heart failure, pulmonary Surgical Intervention
artery catheter placement may be considered, but is usually not
necessary. The primary concept that relates to the optimal choice of ther-
Pain management is titrated aggressively in patients with apy has not changed for nearly 30 years. In most cases, the lo-
dissection. The goals of pain treatment are patient comfort and cation of the dissection determines whether the patient should
decrease in adrenergic tone. Narcotic analgesics are effective in undergo immediate surgery. Type A dissection is treated with
rapid reduction of symptom severity, especially when admin- surgery in virtually all cases, as the outcomes associated with
istered in intravenous form. Long-acting oral formulations of surgical repair are superior to outcomes with medical man-
narcotics are not recommended. agement: 26% versus 50% mortality at 30 days in the IRAD
Blood pressure and dP/dt can be simultaneously decreased series [1]. The one relative contraindication to attempted sur-
with a beta-blocker. Noncardioselective agents such as propra- gical repair of type A dissection is stroke in evolution, due
nolol, labetalol, and esmolol have been used extensively in this to high risk of hemorrhagic transformation of the stroke dur-
context. Beta-blockers should be considered even in patients ing surgery [50]. In aggregate, survival of patients with acute
who are not hypertensive at presentation, as the reduction in type A dissection who are treated with surgical repair has im-
dP/dt is thought to be beneficial in reducing the advancement proved over the last 25 years [51]. Aortic dissection repair is

TA B L E 3 6 . 2
COMMONLY USED MEDICATIONS WITH ROUTES/DOSES

Agents for heart rate and blood pressure reduction in acute aortic syndromes

Class Medication Dosinga

Beta-blockers Metoprolol 2.55.0 mg IV q 5 min, up to three doses followed by 510 mg IV q 46 h


Labetalol 20 mg IV administered over 2 min followed by 4080 mg IV
q 10 min with maximum initial dose 300 mg, to be followed by
2 mg/min IV infusion with 10 mg/min maximum rate
Esmolol 500 g/kg IV bolus dose, followed by 50 g/kg/min IV infusion with 300 g/kg/min
maximum rate
Calcium channel blockers Diltiazem Bolus 510 mg IV, maximum dose 25 mg IV infusion 515 mg/h for up to 24 h
3090 mg PO qid, maximum 360 mg/d
Verapamil 80120 mg PO tidqid maximum 480 mg/d
Nifedipine 1020 mg PO tid, start with 10 mg dose, maximum 180 mg/d
Nicardipine 2040 mg PO tid, start with 20 mg dose, maximum 120 mg/d
Nisoldipine 2040 mg PO qd, start with 10 mg dose, maximum 60 mg/d
Vasodilators Nitroprusside 0.310 g/kg/min IV infusion up to 3 d
a
Therapeutic goals include maintenance of systolic blood pressure 100110 mm Hg, heart rate approximately 60 beats per minute.
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Chapter 36: Acute Aortic Syndromes 363

TA B L E 3 6 . 3
SUMMARY OF ADVANCES IN THE IDENTIFICATION AND MANAGEMENT OF ACUTE AORTIC SYNDROMESa

Risk factors for aortic dissection in patients younger than 40 include familial thoracic aortic aneurysm syndrome (FTAAS);
pregnancy; bicuspid aortic valve; and Marfan, EhlersDanlos, Turner, and Noonan syndromes [1,7,22,28,29]
Risk factors for aortic dissection in older patients include cigarette smoking, hypertension, and atherosclerotic disease [1]
Crack cocaine use has been recently identified as an independent risk factor for aortic dissection, especially in the descending aorta
[25,26]
Preferred treatment for type A dissection is typically urgent surgery, whereas medical management is preferred for type B aortic
dissection, except for those cases involving aortic rupture or branch vessel compromise [1,38]
-Blockade for reduction of dP/dt is critical to the treatment of all the acute aortic syndromes, unless a clear contraindication is
present [1,39,40]
Pericardial tamponade in the context of type A aortic dissection should be treated with definitive surgical correction of the
dissection rather than pericardiocentesis, unless hemodynamic collapse is present, in which case small-volume aspiration of
pericardial fluid may be necessary [40]
Endovascular stent grafting has been used successfully to treat type B dissections, as well as branch vessel disease associated with
both type A and B dissections: this technique is an alternative to intimal flap fenestration [5357]. The Investigation of Stent Grafts
in Aortic Dissection (INSTEAD) study shows no advantage to use of endovascular stents for treatment of chronic type B dissection
[58]
Management strategy of intramural hematoma is informed by location in a manner that mirrors classic dissection: type A
intramural hematoma should be treated surgically, whereas type B intramural hematoma should be treated medically unless another
indication for surgical or endovascular management is present [10,62,74]
The use of biomarkers to differentiate acute aortic syndromes from other etiologies of chest pain is not yet a validated component
of standard clinical practice [4247]
a
Based on recent observational studies.

complex surgery, and each patients medical comorbidities need (IMH) is defined as a spontaneous collection of blood within
to be addressed in detail before surgery as time allows. In the the aortic media that does not apparently communicate with
past, patients older than 80 were thought to have an opera- the lumen. The natural history of IMH is not fully understood.
tive survival rate too low to justify attempted repair. A recent It is thought that it may represent a predecessor of aortic dis-
multicenter study reported acceptable outcomes in aortic dis- section with eventual intimal rupture [48,60].
section repair performed in selected octogenarians. Although Both classic aortic dissection and IMH are generally associ-
this study raises the possibility of aortic dissection repair in ated with the same set of risk factors [9,48] and may be indis-
this age group, this approach remains controversial and each tinguishable clinically [9]. Diagnostic imaging studies, notably
patient must be approached individually [52]. transesophageal echocardiography, CT angiography, or MRI,
Patients with type B dissections are generally managed with- are required to distinguish them (Fig. 36.2). Consequences of
out urgent surgery, as mortality in patients undergoing surgical untreated IMH suggest a similar risk for adverse outcome as
repair is roughly equal to the mortality in those patients treated in typical aortic dissection.
medically [1,38,39]. Typically, patients with type B dissections
are only treated surgically in the context of impending or estab-
lished aortic rupture or branch vessel compromise, especially Epidemiology
with malperfusion. Neither recurrent pain nor severe hyper-
tension has been shown to predict adverse outcome in patients IMH occurs in a minority of the patients presenting with an
with type B dissection of the aorta, and neither alone should apparent aortic dissection. Acute dissection events included in
be considered a primary indication for urgent surgery [53,54]. the IRAD registry were found to be due to IMH 10% of the
Recent studies have investigated the use of percutaneous re- time [1]. Serial imaging of IRAD patients with IMH revealed
pair for managing type B dissection. Although percutaneous that 16% evolved to dissection with intimal tear [48]. There
fenestration of the false lumen had previously been the ther- was no statistically significant difference in mortality rate for
apeutic option of choice in this setting [1], this technique has typical dissection and IMH in this series. Other studies reveal
been largely supplanted by the more definitive endovascular that IMH can progress to typical dissection, as determined by
stent repair. It is thought that the minimally invasive nature of serial scanning, in up to 45% of cases [61].
this technique may decrease perioperative mortality and thus Although the risk factors [9,48] and clinical presentations of
improve outcomes. Initial results and short-term outcomes with classic aortic dissection and IMH are indistinguishable, certain
endovascular therapy of acute type B dissections are promising important differences are recognized. Compared to those with
[5557]. A recently published randomized trial assessing the typical aortic dissection, patients with IMH tend to be older,
impact of endovascular stent grafting in addition to medical tend to have more atherosclerotic disease, and are more likely
therapy in uncomplicated type B dissection revealed no advan- to have a distal acute aortic syndrome; two-thirds of IMH cases
tage with stenting [58]. are type B, in contrast with typical dissections, 65% of which
are type A.
Long-term follow-up of patients with IMH reveals that the
INTRAMURAL HEMATOMA hematoma evolves most commonly into a true or false aor-
tic aneurysm or especially when associated with penetrating
Not all cases of apparent aortic dissection involve communica- atherosclerotic ulcer (PAU). Up to 45% of such aneurysms that
tion between the true and false lumens via a tear in the intima. are located in the ascending aorta lead to rupture [61]. Sponta-
In 1988, the first cases of an atypical form of dissection with- neous regression occurs in up to one-third of cases. Regression
out intimal rupture were described [59]. Intramural hematoma is most likely with IMH not associated with increased aortic
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364 Section III: Cardiovascular Problems and Coronary Care

FIGURE 36.2. CT angiograms demonstrating the typical appearance of a classical aortic dissection,
versus that of an aortic intramural hematoma. Note the smooth crescentic thickening of the wall of
the ascending aorta in the patient with intramural hematoma and the obvious intimal flap seen in the
patient with the acute dissection. [
c Massachusetts General Hospital Thoracic Aortic Center. Used with
permission.]

diameter at the time of presentation [62]. Clinical and radio- hematoma formation. Both of these events could ostensibly be
graphic progression of IMH is more likely when PAU is present at work simultaneously.
(Fig. 36.3). IMH in the absence of PAU appears to follow a
more stable course, especially when located in the descending
thoracic aorta [63].
Clinical Manifestations
The clinical presentation of IMH mirrors that of typical aortic
dissection, and the two cannot be reliably distinguished on the
basis of clinical criteria alone [48].
Etiology and Pathophysiology
There are two proposed mechanisms by which an IMH may
form. The first is the rupture of the vasa vasorum in the aortic Imaging
wall, which may be the result of medial degeneration. The other
leading mechanism is the invasion of a PAU beyond the internal Because the clinical presentation of IMH can overlap with that
elastic lamina of the vessel, compromising the integrity of the of classic dissection, prompt imaging is critical. The same set
media [64,65]. Once in the media, this ulceration can lead to of imaging modalities used for classic aortic dissection is to be

FIGURE 36.3. CT angiogram of an acute penetrating atherosclerotic ulcer, with corresponding pathologic
specimen from the patient after ascending aortic repair.
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Chapter 36: Acute Aortic Syndromes 365

used to image IMH. Some differences in utility exist, and are


worthy of note. As with classic aortic dissection, it is frequently
the case that multiple imaging modalities must be used in a
single patient. As IMH frequently evolves, affected patients
often require serial studies [48].
CXR findings associated with IMH mirror those for classic
aortic dissection. Affected patients may exhibit an abnormal
aortic silhouette or a widened mediastinum, but this finding is
not as well validated as in classic dissection [1,6]. Separation
of intimal calcium from the aortic border may also be visible.
These are simply associated findings; differentiation of IMH H
from classic dissection requires other imaging modalities.
TTE does not allow for definitive, reliable diagnosis of IMH
[9]. With TEE, IMH may appear as an echogenic, crescent-
shaped segment of aortic wall. This is not a definitive modality,
as in some cases, the thickened wall segment can be difficult to
distinguish from atherosclerotic thickening [66]. A
With CT scanning, IMH appears as a crescent-shaped thick-
ening of the aortic wall, but with a normal-appearing aortic
lumen. A contrast study is required for a definitive diagnosis.
The most important feature that distinguishes an IMH from
a classic dissection is the absence of contrast within the aor-
tic wall. MRI allows for diagnosis of IMH without the use of
contrast. The intensity of the hematoma can be determined by
the signal sequence. Aortography is not a useful method for
evaluating IMH, as the sensitivity for identification of IMH is
less than 20% [66].

M
Management
As is the case for management of typical dissection, early imag-
ing and surgical consultation are the central components of the B
management of a patient with an IMH, which can be a rapidly
progressive disease. Frequent reevaluation of the diseased aor-
tic segment may also be warranted, especially if the patient
presents with new hypotension or progressive symptoms. The
most dangerous consequence of IMH is continued expansion
and progression to typical dissection and/or aortic rupture.
Given the high-risk nature of IMH in the ascending aorta,
management is similar to typical aortic dissection: surgery for T
type A syndromes and medical management for type B syn-
dromes [9]. The recent literature contains some controversy
regarding the potential role for medical management of IMH in
the ascending aorta, but at this time, there is no strong evidence
to suggest that medical management is sufficient [48,6772].
For type B IMH, medical management appears to be the
consistently validated early treatment approach, unless a sur-
gical indication is present. In-hospital mortality for patients in
the IRAD series is less than 10% for patients receiving medical
management [48].
There may be a role for prophylactic endovascular stent C
placement in patients with IMH who are thought to be in immi-
nent danger of hematoma expansion and aortic rupture. Type FIGURE 36.4. AC: Endovascular aortic stent grafts for nonsurgical
B IMH should be frequently reassessed and reimaged as in- management of Stanford type B dissection. This patient initially pre-
dicated, as these patients are at increased risk for evolution sented with acute type B dissecting intramural hematoma. Panel A
into classical dissection or rupture [73]. Several studies have shows a contrast-enhanced (CT) scan of the chest demonstrating acute
suggested that a small proportion of IMH will resorb in short- intramural hematoma just inferior to the pulmonary artery bifurcation
with a circumferential, crescentic appearance (H). The IMH extended
term follow-up, and this appears to be correlated with smaller from just distal to the takeoff of the left subclavian artery down to the
aneurysm size at presentation. However, a significant propor- level of the celiac axis. Panel B shows evidence of active hemorrhage
tion of patients will go on to develop enlarging aortic aneurysm into the aortic media (M) at the proximal descending thoracic aorta.
and/or pseudoaneurysm, classic aortic dissection, or rupture Panel C shows a follow-up contrast-enhanced chest CT of the same
[62,74,75]. The role of endovascular stents in preventing these patient at 36 days after initial presentation, with evidence of evolution
late outcomes is currently under investigation [76,77]. The use of the IMH into a classic dissection, with true lumen (T) and filling of
of endovascular stent grafting to manage a complication of a the false lumen at the same level in the proximal descending aorta as
type B IMH with subsequent dissection is demonstrated in Fig- shown in Panel A. (continued)
ure 36.4. A summary of recommended management strategies
for patients with acute aortic dissection or IMH is shown in
Figure 36.5.
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366 Section III: Cardiovascular Problems and Coronary Care

The most commonly encountered aortic aneurysm morphol-


ogy is fusiformspecifically, a symmetrical dilatation of an
aortic segment, involving the entire circumference of the ves-
sel wall (Fig. 36.6). Aneurysms may also be saccular, or may
involve only a portion of the vessel, leading to an asymmet-
ric dilatation. It is also important to distinguish between true
and false aneurysms: a true aneurysm involves all three lay-
ers of the vessel wall, whereas a false aneurysm is typically a
collection of blood underneath the adventitia or outside the
vessel altogether. This collection is frequently the result of a
defect in the aortic wall. The presence of a suspected saccular
aneurysm deserves special note, as it may actually represent a
S false aneurysm caused by a partially contained rupture of the
aortic wall.
Aortic aneurysms are frequently asymptomatic at the time
of diagnosis, and tend to be detected with tests ordered for
D other reasons [83]. Indeed, an aortic aneurysm may not be
associated with any symptoms until the time of rupture. As
the clinical presentations of ruptured thoracic and abdominal
aortic aneurysms (AAAs) frequently differ, they are discussed
separately.
S
C

ANEURYSMS OF THE
THORACIC AORTA
Epidemiology
The overall annual incidence of thoracic aortic aneurysm (TAA)
is 6 per 100,000 [83], and up to 40% of all patients are asymp-
tomatic at the time of diagnosis [84]. The risk of aneurysm
rupture or dissection increases as a function of size. An abrupt
E F increase in risk has been noted at a diameter of 6 cm: for
aneurysms greater than 6 cm, the rupture rate has been ob-
FIGURE 36.4. (Continued) DF: Panel D shows the contrast- served to be 3.7% per year [79]. The most commonly affected
enhanced chest CT scan after placement of a stent graft (S) in the segments are the aortic root and ascending aorta; 60% of ob-
proximal descending aorta at the site of presumed communication be- served cases involve these segments. Aneurysms of the descend-
tween false and true lumen, demonstrating complete exclusion of the ing aorta account for 40% of cases, and the aortic arch ac-
hematoma. Panel E demonstrates a three-dimensional reconstruction of counts for 10%.
the contrast-enhanced CT scan of the aorta in the left anterior oblique The surgical treatment strategy for asymptomatic aortic
view of the same patient 36 days after initial presentation with ex-
travasation of contrast (C) (corresponding to the image in Panel C),
aneurysms differ on the basis of location, size, and etiology: for
and Panel F shows the same left anterior oblique view of the aorta an aneurysm in the aortic root or the ascending aorta, surgical
status-post endovascular stent grafting procedure (S, stent). repair is indicated for a diameter of 5.5 cm or more, although
for patients who are at increased risk of rupture, such as pa-
tients with a bicuspid aortic valve (which is associated with an
intrinsic defect in the medial smooth muscle layer) or Marfan
syndrome, 5 cm (or less in certain cases, such as in patients
EXPANDING AORTIC ANEURYSM with strong family histories for premature aortic dissection or
rupture) is the recommended operative threshold [85,86]. In
AND RUPTURE the descending aorta, surgery is recommended at a diameter of
6 cm or more [82].
Definition and Classification For patients with large TAAs, survival without surgical re-
pair is poor, with 5-year survival after initial identification at
An aortic aneurysm is broadly defined as a segment of the aortic 20%. Rupture occurs in 32% to 68% of patients whose TAAs
lumen whose diameter exceeds 1.5 times the normal diameter are not repaired surgically [87,88]. Of those patients whose
for that segment [78]. The risk of aneurysm rupture increases rupture occurs outside a hospital setting, it is thought that less
as a function of diameter. In addition, rupture risk is thought to than half will arrive to a hospital alive. For those patients who
be higher in rapidly expanding aneurysms [79,80]. Aneurysms survive until hospital admission, mortality at 6 hours is 54%.
are also classified according to location (e.g., thoracic vs. ab- At 24 hours, mortality without surgery is 76% [89].
dominal), morphology, and etiology. All segments of the aorta
can be affected and multiple aneurysms may be found in a sin-
gle patient. Up to 13% of patients with an identified aortic Etiology and Pathophysiology
aneurysm are found to have multiple aneurysm; as such, in
patients in whom a single aneurysm has been detected, consid- Multiple factors have been implicated in the formation of
eration should be given to scanning the entire aorta for addi- TAAs, including atherosclerotic disease, specific gene de-
tional aneurysms [81]. In the general population, abdominal fects, and infectious processes. In many cases, a central
aneurysms are more common than thoracic aneurysms [82]. pathophysiologic process is medial degeneration, which leads
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Chapter 36: Acute Aortic Syndromes 367

Suspected acute aortic syndrome,


based on history, physical exam, chest X-ray

Surgical consultation

Appropriate medical management:


Blood pressure and pain management

CT angiogram or TEE

Positive for aortic rupture Positive for dissection or IMH Negative for dissection or rupture

Emergent
surgery Type A Type B Presence of aneurysm or Normal aorta or
high suspicion presentation low suspicion presentation

Emergent Medical
surgery management Repeat imaging Admission to monitored
study (consider MR), setting with serial
Admission to clinical re-evaluation
ICU setting

Positive for Negative


rupture or type A
dissection

Persistently high
Clinical suspicion
Emergent
surgery

Repeat imaging study


(consider angiogram)

Positive for Negative


rupture or type A
dissection

Serial clinical evaluation


Emergent in ICU setting, consider
surgery urgent exploratory surgery

FIGURE 36.5. A suggested management strategy for patients with suspected acute aortic syndrome.

to the loss of elastic fibers and smooth muscle cells. This pro- aorta is affected and the age at which the abnormality tends to
cess, which is frequently correlated with aging, causes progres- be diagnosed.
sive stiffening and weakening of the vessel wall, leading to pro- Aneurysms in the aortic root and ascending aorta are fre-
gressive dilatation. Hypertension accelerates dilatation due to quently associated with inherited defects in structural genes
the increase in wall strain [82,84,90]. The inciting factor that or with inflammation caused either by infection or by vasculi-
leads to aneurysm formation influences which portion of the tis. In general, aneurysms associated with structural genetic
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368 Section III: Cardiovascular Problems and Coronary Care

FIGURE 36.6. CT angiograms of a fusi-


form aneurysm (left-hand panels, with
dimensions) and a saccular aneurysm
(right-hand panels, white arrows).

mutations tend to occur at a younger age, in some cases during Ascending aortic aneurysm may also be caused by infectious
the second and third decades of life. Identified connective tis- processes, such as bacterial endaortitis or chronic spirochetal
sue disorders, such as Marfan and EhlersDanlos syndromes, infection. Syphilis, once a common cause of aneurysm in the as-
have been established as causes for aneurysms in this portion cending aorta, is now rarely seen in the developed world. The
of the aorta [90,91]. These syndromes are caused by deficits in aortitis caused by bacterial infection leads to both fusiform
fibrillin-1 and type III collagen, respectively. The specific pro- and saccular aneurysms [99]. Inflammation-related aneurysm
tein deficits lead to weakening of the vessel wall due to medial in this area may also be caused by vasculitic processes, most
necrosis with resultant ectasia. A growing body of evidence notably Takayasu or giant cell arteritis [100,101]. Although
reveals a hereditary syndrome (FTAAS) that does not lead to typically associated with stenotic lesions of the aorta or great
overt manifestations of connective tissue disease but is associ- vessels, Takayasu arteritis may present acutely, with the de-
ated with aneurysm of the ascending aorta. Multiple loci have velopment of aortic aneurysms that are associated with signs
been identified, but routine genetic testing for this spectrum of of systemic and focal aortic inflammation; in rare cases, pa-
disorders is not yet available [9295]. A bicuspid aortic valve tients with acute aortic dilatation associated with Takayasu
is also associated with aneurysm of the aortic root/ascending arteritis have suffered acute aortic rupture. Patients with
aorta. Dilatation of this segment of the aorta has been shown to Takayasu arteritis are typically younger Asian females, who
be due to medial degeneration that is independent of the poten- may show involvement of the pulmonary arteries as well. In
tial hemodynamic effects of the abnormal valve. An acquired contrast, aneurysms associated with giant cell arteritis are more
defect in the integrity of fibrillin-1 may also occur in some frequently diagnosed in older Caucasian females with prior
of these patients [96]. A growing body of evidence suggests polymyalgia rheumatica and/or symptomatic temporal arteri-
that the enzymatic activity of several matrix metalloproteinases tis [100102].
(MMPs) may play a central role in the loss of connective tis- Aneurysms in the descending aorta are generally caused by
sue integrity in patients with bicuspid aortic valve [97]. Turner atherosclerosis. As such, these aneurysms are more commonly
syndrome is associated with an increased incidence of bicuspid found in men and are not frequently seen before the sixth
aortic valve, as well as with aortic coarctation and aneurysm decade of life. These aneurysms are found beyond the branch
of the ascending aorta [98]. point of the left subclavian artery and are typically fusiform.
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Chapter 36: Acute Aortic Syndromes 369

Saccular aneurysms may be found at the aortic isthmus, and valuable information, it cannot be considered a definitive study.
are frequently the result of rapid deceleration trauma. TTE allows for the evaluation of the aortic root and ascend-
ing aorta. TEE is well suited to the evaluation of potentially
aneurysmal segments in the aortic arch and descending aorta.
Clinical Manifestations As noted previously, perhaps the most important procedural
drawback regarding TEE is the need for conscious sedation,
Expanding aneurysms of the ascending and descending tho- which may be difficult to administer in a patient who is hemo-
racic aorta produce symptoms due to compression of neigh- dynamically unstable.
boring thoracic structures and compromise of aortic valve CT scanning allows for evaluation of potentially aneurys-
function (see later in the chapter). Compression leads to chest mal segments in the entire aorta. Contrast CT imaging may
and back pain in as many as 37% and 21% of cases, respec- also be helpful in identification of areas of blood extravasa-
tively [103]. Specific thoracic structures, when compressed by tion in ruptured aortic aneurysms. MRI may be used for aortic
the aorta, lead to distinct signs and symptoms, including supe- measurement and identification of aneurysmal segments with-
rior vena cava syndrome, pulmonary symptoms due to tracheal out contrast. Evaluation of blood extravasation with MRI is
compression, or dysphagia due to esophageal compression. In possible, but thought to be less sensitive than CT with con-
addition, stretching of the recurrent laryngeal nerve may lead trast, especially for slow or low-volume extravasation. Aor-
to unilateral vocal cord paralysis, with hoarseness (Ortners tography is a highly sensitive technique for assessing extrava-
syndrome). sation. The use of this technique in the acute setting is ordinarily
Symptoms from rupture of a TAA are largely related to reserved for those cases where neither CT scanning nor MRI is
blood extending into adjoining thoracic spaces. The sudden on- available.
set of acute chest or back pain is a common feature of aneurysm
rupture in all segments of the thoracic aorta. Perhaps the most
salient feature of this pain is the fact that its maximal intensity Rupture of a Thoracic Aortic Aneurysm:
occurs at onset. In patients whose aneurysms have produced
prior symptoms, the pain at the time of rupture may be a more Management
intense form of the same sensation, often at the same location.
The quality of this pain does not necessarily have a tearing Rupture of a TAA is a surgical emergency. Open repair of the
quality, as is often the case with dissection. vessel is the most established repair technique. Typically, the
The most common area of blood flow from a rupture procedure is performed with deep hypothermic circulatory ar-
in the ascending aorta is the left pleural space, followed by rest. The type of repair is determined by the location of the rup-
the intrapericardial space. Blood flow into these areas lead ture and the presence or absence of aortic valve involvement.
to hemothorax and hemopericardium. Tamponade physiology Dacron grafts are generally placed to replace the diseased ves-
may be present. Rupture of the descending aorta can lead to sel segment, with various strategies for aortic valve repair or
erosion into the esophagus: over time, an aortoesophageal fis- replacement when necessary [105]. Recent work indicates that
tula may form, leading to severe hematemesis. No matter where a less invasive form of repair, retrograde endovascular stent
the point of blood egress is found, rapid loss of intravascular placement, may be useful in the repair of aneurysms in the
volume leads promptly to hypotension and shock if unrepaired. descending aorta.
Ancillary warning signs include decreased urine output and Patients with aneurysm of both ascending and descending
altered mental status. segments present an additional challenge. Standard methods
The heart examination may also exhibit distinct abnormal- entail surgical replacement of diseased segments in a staged
ities with expanding aneurysm and rupture. Progressive dilata- fashion; however, newer methods involving a hybrid approach
tion of the aortic root may lead to dilatation of the valve of surgical replacement of the ascending aorta, with subsequent
annulus with consequent signs of aortic regurgitation. This endovascular therapy of the distal segments, appear promising
phenomenon is associated with a diastolic murmur heard best [106].
over the left sternal border with the exception of aneurysms It may be that a particular patient presents with complaints
associated with ectasia of the aortic root, such as syphilitic aor- raising concern for a ruptured aortic aneurysm. In the event
titis, where the murmur of aortic regurgitation may be more that no rupture is found and the patient is hemodynamically
noticeable along the right sternal border. Critical levels of re- stable, it is possible that expansion of the aneurysm is respon-
gurgitation may be associated with left-sided heart failure. This sible for the symptoms. In such a case, the focus of immediate
murmur may be present in the absence of rupture. When rup- clinical treatment should be to decrease aortic wall strain and
ture of one of the sinuses of Valsalva occurs, the murmur may systemic blood pressure through the use of beta-blockers in the
be continuous; in this setting, the ruptured area may commu- context of a critical care setting. Prompt surgical consultation
nicate with a cardiac chamber, such as the right atrium or plays a vital role in the continuing care of these patients.
ventricle.
In the context of acute rupture, the electrocardiography fre-
quently shows evidence of ventricular strain or ischemia. ANEURYSMS OF THE
Over time, markers of myocardial necrosis may be elevated as
well. Several studies show an elevation in d-dimer in the con-
ABDOMINAL AORTA
text of aortic dissection, but elevation of this marker has not
yet been validated in aneurysm progression or rupture [104]. Epidemiology
There is currently no widely available biomarker in use to de-
tect vascular injury in the context of aneurysm or rupture. AAAs are far more common than TAAs. The estimated preva-
lence of AAAs ranges between 1.3% and 8.9% in men and
between 1.0% and 2.2% in women older than 60 years [107
Imaging 110]. Most cases are observed in men older than 55 years
and women older than 70 years. AAAs have been found to be
Aortic aneurysm may be visualized as a widened mediastinum correlated with smoking [111]. Overall prevalence of abdom-
on anteroposterior views. Although this technique offers in- inal aneurysms has risen substantially over the past 30 years
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370 Section III: Cardiovascular Problems and Coronary Care

[112]. This trend has been linked to the increased prevalence arteritis or Behcets disease, may be associated with abdominal
of atherosclerosis, which is thought to be the major etiology re- aneurysms [120,121].
sponsible for abdominal aneurysms. In addition, improvements
in imaging technology have increased the rate of detection.
Rupture of AAAs is estimated to cause approximately Clinical Manifestations
15,000 deaths per year in the United States [112,113]. The
total mortality rate for patients with rupture ranges from 65% As is the case with thoracic aneurysms, most abdominal
to 85% [107]. One prospective study revealed that 25% of aneurysms are asymptomatic and tend to be discovered with
patients with AAA rupture die before arriving at a hospital. testing performed for other reasons. Those patients who do
Of those who arrived at the hospital alive, 51% died before have aneurysm-related complaints tend to report pain in the
surgery. Patients who did have surgery sustained a 46% oper- hypogastric area and/or pain in the lower back. This pain is
ative mortality rate. Total 30-day survival rate for this popula- caused by the expansion of the aneurysm and tends to last for
tion was 11% [80]. Given the poor prognosis associated with hours or days at a time, and is usually dull and steady. In the
rupture, elective repair is recommended when possible. As is abdomen, fewer structures tend to be affected by the expanding
the case with TAAs, the risk of rupture increases as a function aorta. The most common consequence of aortic expansion is
of aortic diameter. Recently published guidelines recommend compression of the ureter or kidney, leading to hydronephrosis
elective surgery for AAA 5.5 cm or more in men and 5 cm in or potentially renal failure.
women [114]. An episode of rupture tends to be announced by a sudden
onset or increase in abdominal and/or back pain. The most
notable feature of this pain is that it is at its maximum at the
Etiology and Pathophysiology time of onset. Rupture most frequently leads to blood leakage
into the left retroperitoneal space. These patients may present
Incidence of AAA is closely correlated with the presence of with an initial episode of pain associated with the first rup-
atherosclerotic disease in the aorta. In general, the infrarenal ture, followed by temporary tamponade of the retroperitoneal
segment of the aorta is most heavily affected by atherosclerosis, space. A larger, life-threatening bleed inevitably follows. Less
and this is also the segment where most abdominal aneurysms frequently, the aneurysm may erode into surrounding struc-
are observed. These aneurysms are typically fusiform, but sac- tures, most notably the duodenum, leading to either formation
cular aneurysms may also be found. of an aortoduodenal fistula or potentially massive gastrointesti-
The risk factor most closely associated with abdominal nal (GI) bleeding [113,122].
aneurysms is smoking, followed by age, hypertension, and hy- Physical examination of a patient with an AAA may re-
perlipidemia [115]. There is also a strong association between veal a palpable, pulsatile mass in the midline. This mass is
gender and abdominal aneurysm formation [108]. Family his- easiest to palpate in the hypogastric or paraumbilical region.
tory of AAA is associated with a 30% increase in risk for AAA The sensitivity of the manual examination is suboptimal: 82%
formation, but there are not yet any specific genes linked with for aneurysms 5 cm or greater. Furthermore, a mass may be
this finding [82,116]. difficult to appreciate [123]. Consequently, the absence of a
Damage to the vessel wall, caused by atherosclerotic plaque, pulsatile mass on physical examination should not be inter-
has been shown to cause local inflammation. This inflamma- preted as an absence of aneurysm. On rupture of an abdominal
tory process is thought to cause degradation of extracellular aneurysm, most patients become hypotensive, tachycardic, and
matrix proteins, notably elastin and collagen. In addition, it is diaphoretic. Patients may also exhibit signs of peritoneal irri-
thought that the proinflammatory cytokine milieu leads to cell tation on examination. As noted, the patient may also present
death in the vessel wall. Weakening of the vessel wall follows, with evidence of GI bleeding. Laboratory analysis may reveal
potentially accelerated by the action of multiple proteases, in- evidence of elevation in d-dimer or an elevation in cardiac
cluding MMP and cathepsin L [117,118]. There is some specu- biomarkers, due to demand-related myocardial ischemia.
lation that MMP polymorphisms may lead to a change in sus-
ceptibility to abdominal aneurysms, but there are no screening
tests currently available to the clinician [119]. Hypertension
increases the wall strain on the weakened vessel wall, lead- Imaging
ing to accelerated expansion. The full effects of smoking on
X-ray plain film is not an adequately sensitive technique for the
aneurysm formation and expansion are not known, but in-
assessment of AAAs. Echocardiography is not helpful for the
creased atherosclerosis and hypertension are thought to be con-
evaluation for extrathoracic segments of the aorta. Transcuta-
tributors.
neous ultrasound is a noninvasive and readily available tech-
Aneurysms in the descending thoracic aorta tend to be
nique for the evaluation of the abdominal aorta. This method
caused by atherosclerosis. These aneurysms often extend into
is frequently used to track the size of abdominal aneurysms,
the abdominal cavity, superior to the renal arteries. Such
though it is not the imaging modality of choice for the acute
aneurysms are referred to as thoracoabdominal, and their man-
aortic syndromes. Like TTE, abdominal ultrasound is often
agement mirrors the management of aneurysms in the abdom-
limited by body habitus. As with thoracic aneurysms, the most
inal cavity.
definitive evaluations are provided by CT scanning and MRI.
Aneurysms in the descending thoracic or abdominal aorta
Aortography may provide useful information regarding aor-
may also be caused by acute bacterial infections. This is not
tic aneurysm, but it is not the modality of choice in the acute
a common finding, but tends to be found more often in pa-
setting unless CT scanning and MRI are not available.
tients who are intravenous drug users or who have traveled
recently from a country where exposure to typical organisms
(Salmonella and Brucella) is more likely to occur. Chronic
tuberculosis is rarely associated with abdominal aneurysms. Rupture of an Abdominal Aortic Aneurysm:
Syphilis may also be associated with abdominal aneurysms, Management
but it is more commonly associated with the ascending aorta.
Connective tissue disorders, such as Marfan and EhlersDanlos Rupture of an AAA is a surgical emergency. Open repair, with
syndromes, do not typically affect the abdominal aorta; how- replacement of the diseased segment with a Dacron graft, is
ever, some systemic inflammatory disorders, notably Takayasu the most established technique. Intraoperative mortality after
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Chapter 36: Acute Aortic Syndromes 371

rupture is very high, as noted previously. Retrograde endovas- Timely, but elective, surgical or endovascular intervention on
cular stent placement is a promising technique [124126], but the basis of size criteria, as assessed with longitudinal imaging,
it is not yet in common use in the acute setting [127,128]. is the most effective means to prevent progression to rupture.

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CHAPTER 37 EVALUATION AND


MANAGEMENT OF HYPERTENSION IN THE
INTENSIVE CARE UNIT
BENJAMIN M. SCIRICA AND ROBERT J. HEYKA

endocrine causes [3] are found in a significant percentage of


HYPERTENSIVE URGENCIES patients with hypertensive crisis.
AND EMERGENCIES In hypertensive crises, the elevation in BP tends to be severe
with diastolic blood pressures (DBPs) greater than 120 mm
Patients with elevated blood pressure (BP) in the intensive care Hg. However, the level of systolic blood pressure (SBP), DBP,
unit (ICU) present with either a BP that threatens to cause or mean arterial pressure (MAP) does not distinguish them.
imminent target organ damage (TOD) to vascular beds or a Rather, it is the presence or absence of acute and progressive
transient, usually more benign elevation in BP without threat TOD [4,5].
of TOD. Hypertensive emergency means the BP elevation is asso-
ciated with ongoing neurologic, myocardial, vascular, hema-
tologic, or renal TOD, whereas hypertensive urgency means
Definitions that the potential for TOD is great and likely to occur if BP
is not soon controlled. Examples of hypertensive emergencies
Hypertensive syndromes have diverse etiologies and often have are provided in Table 37.1. In many instances, a better term
little in common besides a similar presentation. The terms used for urgencies is simply uncontrolled BP [4,5]. Many patients
to describe these clinical syndromes are mostly of historic sig- present to emergency rooms with inadequately treated BP and
nificance. In original usage, they applied to specific clinical find- no evidence of TOD [6]. There is no evidence of benefit from
ings often without an appreciation of their systemic abnormal- rapid reduction in BP in these asymptomatic patients [7], and
ities. They are often misapplied. Hypertensive crisis is loosely their difficult-to-control hypertension can be evaluated as out-
defined as any clinical situation with a severe elevation in BP patients [8].
[1]. Hypertensive emergencies and urgencies are categories of Accelerated and malignant hypertensions are older terms
hypertensive crisis that may be life threatening and occur (a) named on the basis of ophthalmologic findings and refer to
against the background of worsening chronic essential hyper- categories of hypertensive crises with exudative retinopathy,
tension, (b) with secondary forms of hypertension, or (c) in retinal hemorrhages, or papilledema. They probably represent
patients without previously known hypertensive disease. a continuum of organ damage [9].
There are not reliable data regarding the actual yearly num- Accelerated hypertension may be an urgency or emergency
ber of hypertensive emergencies; however in the United States, with grade III KeithWagenerBarker retinopathy: that is, con-
hypertension is the primary diagnosis in more than 500,000 striction and sclerosis (i.e., grades I or II) plus hemorrhages and
hospital admission [1]. Patients with essential hypertension exudates (grade III). The presence of exudate is more worri-
who present to emergency rooms with hypertensive crises tend some than hemorrhage alone. Malignant hypertension is grade
to be aware of their diagnosis of hypertension, on medication IV KeithWagenerBarker retinopathy and with papilledema
but noncompliant, are African-American or Hispanic, young that signifies central nervous system (CNS) involvement, is a
males, and of lower socioeconomic status [2]. Other secondary hypertensive emergency. It is frequently associated with diffuse
forms of hypertension, including renovascular disease or TOD, such as hypertensive encephalopathy, left ventricular
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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374 Section III: Cardiovascular Problems and Coronary Care

TA B L E 3 7 . 1 may develop a hypertensive crisis with acute conditions such


as acute vasculitis, subarachnoid hemorrhage (SAH), unstable
EXAMPLES OF HYPERTENSIVE EMERGENCIES angina, or eclampsia at lower systemic BP.
Cerebral circulation is the most sensitive vascular bed to
Severely elevated blood pressure and the presence of: breakthrough and ischemia [13]. Cardiac perfusion tolerates a
Acute ischemic stroke more pronounced drop in BP, even with underlying atheroscle-
Acute hemorrhagic stroke/subarachnoid hemorrhage rotic disease, because myocardial oxygen demands decrease
Acute myocardial infarction dramatically when pressures decrease. In organ beds such as
Acute pulmonary edema the kidneys with antecedent atherosclerotic, acute BP changes
Acute aortic dissection are less tolerated and may worsen renal perfusion [4,5].
Encephalopathy In most patients with hypertensive crises, the pathophysio-
Perioperative hypertension logic abnormality is an increase in systemic vascular resistance
Postoperative bleeding (SVR), not an increased cardiac output (CO) (MAP = CO
Severe epistaxis SVR). The increase in SVR elevates BP, overrides local autoreg-
Eclampsia ulation, and leads to organ ischemia.
Pheochromocytoma crisis
Recreational drug abuse with cocaine, lysergic acid
diethylamide (LSD), ecstasy, amphetamines APPROACH TO THE PATIENT
Acute renal failure
Hemolytic anemia In the ICU, therapy must often begin before a comprehensive
Monoamineoxidase inhibitor interactions patient evaluation is completed. A systematic approach offers
the opportunity to be expeditious and inclusive (Table 37.2).
A brief history and physical examination should assess the
degree of TOD and rule out obvious secondary causes of hyper-
failure, renal fibrinoid necrosis, or microangiopathic hemolytic tension. The history should include prior hypertension, other
anemia. In the 1930s, the term malignant was given to reflect significant medical disease, medication use, compliance, recre-
the dismal survival among these patients, approximately 60% ational drugs use, and, most importantly, symptoms from TOD
at 2 years after diagnosis and less than 7% at 10 years. With to neurologic, cardiac, or renal systems. Examination should
the introduction of effective hypertensive therapy, the progno- verify BP readings in both arms, supine and standing, if pos-
sis has significantly improved, with a 5-year survival of 74%. sible and eliminate the rare but important finding of pseu-
The most common causes of death are renal failure (40%), dohypertension due to extensive arterial calcification using
stroke (24%), myocardial infarction (11%), and heart failure Oslers maneuver, which is performed by inflating the BP cuff
(10%) [10]. to greater than the brachial systolic BP. A palpable radial or
brachial artery, despite being pulseless, signifies a significantly
stiff artery and the likely overestimation of the true BP [14].
IMPORTANCE OF TARGET Intra-arterial monitoring may be necessary to verify readings
ORGAN DAMAGE and monitor treatment. Also include direct ophthalmologic ex-
amination looking for hemorrhages, exudates, or papilledema;
Most organ beds can regulate the amount of blood flow they auscultation of the lungs and heart; and evaluation of the ab-
receive over a wide range of systemic pressures by autoregu- domen for masses or bruits and the peripheral pulses for bruits,
lation: OBF = OPPr/OVR, where OBF is organ blood flow, masses, or deficits. Signs of neurologic ischemia include altered
OPPr is organ perfusion pressure, and OVR is organ vascu-
lar resistance [11]. Small arteries and arterioles constrict or
dilate in response to local myogenic effectors acting on the en- TA B L E 3 7 . 2
dothelium that respond to transmural (perfusion) pressure gra- INITIAL EVALUATION OF HYPERTENSIVE CRISIS IN
dients. A decrease in OPPr leads to vasodilation; an increase THE INTENSIVE CARE UNIT
in OPPr leads to vasoconstriction and limits pressure-induced
damage when systemic pressure rises. The cerebral circulation 1. Continuous blood pressure monitoring
can maintain perfusion with changes in MAP from about 60 to a. Direct (intra-arterial)preferred
150 mm Hg [11]. When MAP exceeds the usual autoregulatory b. Indirect (cuff)
range, breakthrough or loss of autoregulation occurs. 2. Brief initial evaluation, including history and physical
Sustained BP greater than the usual autoregulatory range examination with attention to
leads to damage of the endothelial lining of capillaries and ar- a. Neurologic including funduscopic examination and
terioles, resulting in leakage of plasma into the vascular wall. cardiac, pulmonary, renal symptoms
Fibrin deposition reduces lumen diameters and precipitates lo- b. Assessment of organ perfusion and function (e.g.,
cal edema and sclerosis. In patients with chronic hypertension, mental status, heart failure, urine output)
the loss of autoregulation typically occurs only at extremely c. Blood and urine studieselectrolytes, blood urea
elevated BPs, whereas in patients without any significant hy- nitrogen, creatinine, complete blood cell count with
pertension, in whom the protective autoregulation has not de- differential, urinalysis with sediment; if indicated, serum
veloped, edema and the consequent organ-specific symptoms catecholamines, cardiac enzymes
can be seen with DBPs greater than 100 mm Hg [12]. d. Electrocardiogram (assess for strain or ischemia)
When OPPr falls to lesser than the lower limits of autoreg- e. Chest radiograph (assess size of aorta, cardiomegaly, or
ulation, organ ischemia and infarction may occur. Limits of heart failure)
critical perfusion pressure and tolerance to variation in OPPr 3. Initiation of therapy (within 1 h of presentation if TOD is
vary among individuals. The elderly or patients with chronic identified)
hypertension tolerate an elevated MAP because of an upward 4. Further evaluation of etiology once stabilized
shift in their cerebral autoregulation curve but have a dimin-
ished tolerance to hypotension with vessel functional and struc- TOD, target organ damage.
tural changes [12]. Patients without antecedent hypertension
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 37: Evaluation and Management of Hypertension in the Intensive Care Unit 375

mental status, headaches, nausea, and vomiting in addition TA B L E 3 7 . 3


to focal neurologic deficits. Ancillary evaluation should in-
clude electrolytes, blood urea nitrogen and creatinine, complete PARENTERAL VERSUS ORAL THERAPY OF
blood cell count with differential, or echocardiogram (ECG), HYPERTENSION IN THE INTENSIVE CARE UNIT
chest radiograph, and assessment of recent urine output. As
the patients condition stabilizes, further evaluation of unex- Is this a hypertensive emergency?
plored reasons for the hypertensive crisis can be considered and Is rapid onset of effect needed?
pursued. Is rapid lowering of blood pressure needed?
Is a shorter duration of action important?
Is the patient at risk for overshoot hypotension?
Patients with Neurologic Symptoms Atherosclerotic heart disease
Renovascular hypertension
In patients with neurologic symptoms, a noncontrast computed Cerebrovascular disease
tomogram of the head is important to exclude intracerebral Dehydration
hemorrhages (ICHs) or mass effect. Magnetic resonance imag- Other recent antihypertensive therapy
ing is more sensitive for detecting early ischemic strokes, as well
as the edema and white matter changes in the parieto-occipital
region (posterior leukoencephalopathy syndrome) associated
with hypertensive encephalopathy [15]. Early identification of bilizes. Because the ICU is an artificial environment, physi-
acute vascular events such as ischemic strokes or ICHs is criti- cians should avoid attempts to normalize BP especially if large
cal as early management and BP goals differ from hypertensive doses of medications are required. Further fine-tuning of BP
encephalopathy. to levels suggested by Joint National Committee VII [6] or the
European Society of Hypertension/European Society of Car-
diology guidelines for the management of hypertension [21]
TREATMENT should occur once the patient resumes his or her usual diet,
activity, and compliance at home.
Most studies of hypertensive emergencies are either nonran-
domized or suffer from (a) tremendous variation and incon-
sistency in definitions and cutoffs, (b) absence of important SPECIFIC HYPERTENSIVE CRISES
and long-term outcomes such as mortality, (c) being under-
powered with wide confidence intervals, and (d) inconsistent
reporting of adverse effects. Thus, treatment recommendations Acute Left Ventricular Heart Failure
for hypertensive emergencies are not based on a large body
of randomized controlled studies. One systematic review of Decreases in SVR and MAP improve left ventricular function
hypertensive urgencies and emergencies studies found no evi- by decreasing cardiac work, left ventricular wall tension, and
dence supporting any one agent over another. For hypertensive oxygen demand. Intravenous nitroglycerin or nitroprusside are
emergencies, nitroprusside, captopril, and clonidine were ac- the agents of choice in acute heart failure because they rapidly
ceptable choices. For urgencies, a number of agents were used reduce preload and diminish pulmonary congestion [20]. Ni-
and effective [16]. A systematic review for the Cochrane col- troprusside, a balanced vasodilation with a decrease in both
laboration, which included more recent studies, again failed preload and afterload, is usually administered with other acute
to detect any specific agent or strategy that was superior to therapy for pulmonary edema, such as diuretics. Nitroglycerin
another. There was well-documented efficacy for BP reduction has greater effect on the venous (preload) side than on the arte-
with nitrates (including nitroprusside), angiotensin-converting rial side. Nitroglycerin is preferred for management of ischemic
enzyme (ACE) inhibitors, diuretics, -adrenergic antagonist, heart failure [20]. Because of the fairly rapid development of
calcium channel blockers, and dopamine agonists [17]. Given tachyphylaxis to nitrates, alternative and more chronic therapy
this lack of data to guide therapy, how should we proceed? should be instituted within 24 hours of initiation of therapy.
The intensity of intervention must be determined by the clin- The use of an intravenous ACE inhibitor in this situation is con-
ical situation. In many situations, intubation, seizure control, traindicated though oral agents can be resumed or initiated.
hemodynamic monitoring, and maintenance of urine output
can be as important as control of BP. Initial therapy should
terminate ongoing TOD, not return BP to normal. Because Myocardial Ischemia or Infarction
cerebral circulation is the most sensitive to ischemia, the lower
limit of cerebral autoregulation for each patient determines the Treatment of elevated BP is only part of the overall therapy
initial goal. This floor is approximately 25% lesser than the to preserve and restore cardiac perfusion with anti-ischemic
initial MAP or a DBP in the range of 100 to 110 mm Hg [11]. medications, antithrombotic agents, thrombolytic therapy, per-
Reasonable initial therapy is to decrease MAP by 25% with an cutaneous coronary intervention, or surgery. Therapy should
agent that decreases SVR, considering the medical history, ini- maintain local coronary arterial flow and not induce a steal syn-
tiating events, and ongoing TOD [5]. Patients with acute left drome with differential relaxation of coronary vessels. Because
ventricular failure, myocardial ischemia, or aortic dissection nitroprusside may actually divert the flow away from post-
require more aggressive treatment [1820]. stenotic areas, nitroglycerin is preferred. Beta-blockers given
The decision to use oral or parenteral therapy depends intravenously also act to maintain coronary perfusion in the
on several factors. Atherosclerotic disease puts the patient at face of decreased systemic pressures and decrease myocar-
higher risk if therapy overshoots the mark. The answers to the dial oxygen demand by lowering heart rate and BP. The use
questions in Table 37.3 guides the decision of parenteral versus of an intravenous ACE inhibitor in patients with an acute
oral therapy. Table 37.4 lists recommendations and precautions myocardial infarction and depressed left ventricular function
for therapeutic agents, and Table 37.5 lists proper dosing for should be avoided as it may precipitate symptomatic hypoten-
each agent. sion. Uncontrolled hypertension (SBP >180 mm Hg or DBP
Once the patient is stable, additional diagnostic studies may >110 mm Hg) is a relative contraindication to treatment with
proceed. An oral regimen can be started as the situation sta- fibrinolytic treatment [18].
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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376 Section III: Cardiovascular Problems and Coronary Care

TA B L E 3 7 . 4
TREATMENT OF HYPERTENSIVE EMERGENCIES

Type Recommended drugs Target of treatment

Neurologic
Hypertensive encephalopathy Nimodipine, labetalol 15%25% decrease in MAP over 36 h
Intracerebral hemorrhage or Nitroprusside, labetalol, nicardipine Same (debated)
subarachnoid hemorrhage
Cerebral infarction Nitroprusside, labetalol, nimodipine, nicardipine Same (debated)
Head injury Nitroprusside Same
Cardiovascular
Myocardial ischemia, infarction Nitroglycerin, beta-blockers, labetalol Control of ischemia
Aortic dissection Beta-blockers, nitroprusside, labetalol Goal of SBP 120 mm Hg in 2030 min
Acute left ventricular failure Nitroprusside, nitroglycerin, loop diuretics, Improved Sx
converting enzyme inhibitors
Renal failure
Acute renal failure Fenoldopam, nitroprusside, labetalol Decrease MAP 25%
Other
Hemorrhagic Nitroprusside, labetalol, others as needed Control risk of bleeding
Malignant hypertension As with encephalopathy; oral agents
may be considered
Obstetric Hydralazine, methyldopa, MgSO4 DBP <90 mm Hg

DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure; Sx, signs and symptoms.

Aortic Dissection Ischemic Stroke


Aortic dissection is the most common acute aortic syndrome. It Elevated BP is common in patients presenting with acute is-
is imperative to begin therapy for aortic dissection immediately chemic strokes. Both low and high BPs are associated with
to prevent extension or rupture, regardless of the ultimate ther- poor outcomes. For every increase in 10 mm Hg greater than
apy. Uncomplicated acute type B dissection is usually treated 180, there is a 40% increase in the risk of worsening neuro-
with medication. Therapy is directed to lower BP and the rate logic status [24]. Once ischemia occurs, a central core of dense
of the rise of pressure (d p/dt). BP should be lowered rapidly ischemia of variable size is surrounded by less severe ischemia
to the lowest level, permitting continued good organ perfusion that can potentially be salvaged, termed the ischemic penumbra
(i.e., no change in mental status or new neurologic symptoms [25]. This area of stunned, but viable, tissue depends on contin-
and continued urine output). Intravenous beta-blockade is the ued blood flow and may need higher pressures for continued
initial therapy of choice, in particular with labetalol or esmolol. perfusion. Because of the concern about abrupt reduction in
Any acute therapy that decreases BP without also decreasing BP in patients presenting with acute strokes has led the Ameri-
d p/dt or induces reflex tachycardia can extend the dissection can Heart Association and American Stoke Association guide-
and should be avoided. Once beta-blockade is started, vasodi- lines for the early management of adults with ischemic stroke
lation with nitroprusside can be added if necessary [19,22]. give a consensus recommendation that emergency use of BP-
lowering agents should be withheld unless the DBP is greater
than 120 mm Hg or the SBP is greater than 220 mm Hg. In
patients who are potentially eligible for reperfusion therapy,
Hypertensive Encephalopathy it is recommended to consider therapy for levels greater than
185 mm Hg SBP or 110 mm Hg DBP with labetalol, nitroprus-
Hypertensive encephalopathy occurs with severe BP elevation side, or nicardipine. Thrombolytic therapy should not be given
as cerebral autoregulation is overwhelmed and can lead to if the BP remains elevated to greater than 185/110 mm Hg.
blindness, seizures, coma, and death. Pathologic findings in- After reperfusion therapy, labetalol or nicardipine is recom-
clude endothelial dysfunction, cerebral edema, petechial hem- mended for SBP levels greater than 180 mm Hg or DBP levels
orrhages, and microinfarcts [11]. The typical patient has greater than 105 mm Hg and nitroprusside for SBP levels about
chronic untreated hypertension and the slow development 230 mm Hg [24]. If clinical deterioration is noted with BP
of neurologic symptoms, especially headaches, over 48 to reduction, higher BPs must be accepted.
72 hours. Hypertensive encephalopathy is much less common
with better access to antihypertensive medication. Any degree
of control of hypertension can dramatically decrease the likeli-
hood of encephalopathy. As mentioned previously in the chap- Subarachnoid Hemorrhage
ter, patients with severe hypertension and neurologic symptoms
should have neuroimaging to exclude acute ischemic strokes The treatment of SAH is complicated and unsettled. It is un-
or hemorrhages, in which the goals of hypertension manage- clear if uncontrolled hypertension increases the risk of re-
ment differ from hypertensive encephalopathy. Treatment with bleeding [26,27]. A Cochrane review found that oral, but not
short-acting parenteral agents should lead to rapid resolu- intravenous, calcium channel blockers (CCB) reduce the risk of
tion of symptoms. Continued symptoms suggest other CNS poor outcome and secondary ischemia [28], which is based pri-
pathology [23]. marily on studies using nimodipine. If vasospasm occurs later,
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 37: Evaluation and Management of Hypertension in the Intensive Care Unit 377

TA B L E 3 7 . 5
PROPER DOSING FOR AGENTS TO TREAT HYPERTENSIVE CRISIS

Agent Administration Onset Duration Special indications

Direct vasodilators
Nitroprusside IV infusion: 0.2510.0 g/kg/min Immediate 12 min Hypertensive emergencies
Nitroglycerin IV infusion: 5200 g/kg/min 25 min 510 min Heart failure or cardiac ischemia
Fenoldopam IV infusion: 0.1 g/kg/min uptitrated by 515 min 30 min Most hypertensive emergencies;
0.050.1 g/kg/min increments to avoid in glaucoma
maximum 1.6 g/kg/min
Hydralazine IV bolus: 1020 mg 1020 min 14 h Eclampsia
Adrenergic blockers
Phentolamine IV 515 mg 12 min 1020 min Pheochromocytoma,
catecholamine surge
Esmolol IV bolus 250500 g /kg/min IV 510 min 1030 min Most hypertensive emergencies
bolusrepeat after 5 min
IV infusion 50100 mg/kg/min; give new
bolus when increase infusion
Labetalol IV bolus: 2080 mg q10 min 510 min 36 h Most hypertensive emergencies;
IV infusion: 0.52 mg/min not in decompensated heart
failure
Calcium antagonists
Nicardipine IV infusion: 515 mg/h 510 min 12 h Most hypertensive emergencies;
not in heart failure
Nimodipine IV infusion: 510 mg/h by mg/h, up to 1530 min 36 h Subarachnoid hemorrhage
15 mg q30 min, 60 mg q4h 21 d; repeat
Clevidipine IV infusion: 12 mg/h, double dose q90 s. As 24 min 515 min Most hypertensive emergencies
approach goal BP, by less than double
and lengthen uptitration to q510 min.
Typical goal is 46 mg/h
Angiotensin-converting enzyme inhibitors
Captopril PO 6.2525 mg, repeat q30 min, if necessary 1h 14 h
Enalaprilat IV bolus: 1.255.0 mg (over 5 min) q6h 1530 min 68 h Acute left ventricular failure; not
in myocardial infarction
Central-acting agonists
Clonidine PO 0.2 mg initially; 0.2 mg/h (total 0.7 mg) 3h
Miscellaneous
Trimethaphan IV infusion: 0.55 mg/min 15 min 515 min

IV, intravenous; PO, oral.

increases in BP with triple-H therapy (hypervolemia, hyper-


tension, and hemodilution) is recommended but not proven ELEVATED BLOOD PRESSURE
[26].
WITHOUT HYPERTENSIVE CRISIS
Elevated BP is seen in the ICU without TOD. Patients may re-
Intracerebral Hemorrhage quire treatment of (a) chronic hypertension; (b) new, transient,
and usually mild elevations in BP; or (c) elevated BP in the pe-
Similar cautions apply to ICH. BP is often markedly elevated rioperative setting. The goal of treatment is not based solely on
in patients with ICH. With severely elevated BP and neurologic BP readings, but on an appreciation of the acute and chronic
symptoms, the differentiation of structural pathology from care of the patient [5].
hypertensive encephalopathy can be difficult. The American
Heart Association and American Stroke Association guidelines
for the treatment of ICH acknowledge the lack of randomized
trial data to guide therapy, but recommend initiation of ther- Continued Therapy of Chronic Hypertension
apy for (i) SBP levels greater than 200 mm Hg or MAP greater
than 150 mm Hg and (ii) SBP levels greater than 180 mm Hg Patients in the ICU often have a history of hypertension. BP
or MAP greater than 130 mm Hg, with evidence of increased levels may rise if the patient is unable to continue his or her
intracerebral pressures to maintain a perfusing pressure of usual antihypertensive regimen; therefore, alternative agents
60 mm Hg or more. In patients with SBP levels greater than should be instituted. BP elevation in patients who have recently
180 mm Hg or MAP greater than 130 mm Hg without any ev- discontinued chronic therapy can be severe and present as re-
idence of elevated intracerebral pressures, a target of an MAP bound or discontinuation syndrome. The likelihood of rebound
of 110 mm Hg or BP of 160/90 mm Hg is likely beneficial [29]. hypertension is proportional to the prior dose of medication.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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378 Section III: Cardiovascular Problems and Coronary Care

TA B L E 3 7 . 6 TA B L E 3 7 . 7
NEW ONSET OF HYPERTENSION IN THE INTENSIVE HYPERTENSION WITH CARDIOVASCULAR SURGERY
CARE UNIT
Preoperative period
Situational Anxiety
Pain Pain
Anxiety Angina
New-onset angina Discontinuation of antihypertensive or cardiac therapy
Hypocarbia Rebound hypertension
Hypoxemia Intraoperative period
Hypothermia with shivering Induction of anesthesia
Rigors Drug effectsvasodilation, inotropic changes
Volume overload Manipulation of viscera or trachea, urethra, and rectum
Rebound or discontinuation syndrome Sternotomy, chest retraction
Prior, undiagnosed, untreated hypertension With initiation of cardiopulmonary bypass
Postoperative period
Early (02 h)
Hypoxemia, hypercarbia, hypothermia with shivering,
Hypotension may develop in patients with chronic hyper- postanesthetic excitement or pain
tension who were noncompliant with medication but have all After myocardial revascularization, valve replacement,
medications given as prescribed on admission. BP may drop repair of aortic coarctation
and require ICU admission for volume and pressor support. Intermediate (1236 h)
If noncompliance is suspected, it is better to start with lower As given previously
doses and adjust upward. Fluid overload, mobilization
Reaction to endotracheal, nasogastric, chest, or bladder
tube
New Onset of Hypertension
New and usually temporary increases in BP may occur in
the ICU. Many factors may cause short-term elevations in BP
(Table 37.6). Low doses of short-acting agents should be used PHARMACOLOGIC AGENTS
to avoid sharp drops in BP in this usually self-limited situa-
The choice between parenteral and oral therapy rests on the
tion. Undiagnosed essential or secondary hypertension should
answers to several questions (Table 37.3). In a true hyperten-
be considered especially if evidence of TOD is present.
sive emergency, parenteral therapy with arterial BP monitoring
offers a more controlled onset and offset of effect (Table 37.5).
The following are summary statements of available agents
Perioperative Hypertension and are not meant to be inclusive. Additional information on
the pharmacology of available agents can be found elsewhere
Uncontrolled BP can induce new TOD, can increase the risk [6,16,18,21,23,3537].
of vascular suture breakdown or bleeding, and may worsen
overall prognosis.
Direct Vasodilators
Preoperative Evaluation
Sodium Nitroprusside
Moderate chronic hypertension is not a major risk factor for
surgery in otherwise stable patients, but it is a marker for po- Sodium nitroprusside has the longest track record for the treat-
tential coronary artery disease (CAD) [30]. Routine BP therapy ment of severe hypertension. It dilates both arterioles and
should be continued as usual up to the morning of surgery and venules, reduces afterload and preload, and lowers myocardial
resumed either orally or intravenously as soon as possible post- oxygen demand. Its effects are mediated by intracellular cyclic
operatively. Surgery should probably be delayed if BP is greater guanosine monophosphate and nitric oxide in an endothelial-
than 180/110 mm Hg in patient with CAD [31]. independent mechanism shared with other nitrosovasodilators.
Nitroprusside has rapid onset and offset of action. Drug resis-
tance is rarely observed. Nitroprusside is rapidly decomposed
Perioperative Hypertension nonenzymatically in the blood to cyanide, which is then con-
verted into thiocyanate in the liver. At high doses, acute toxicity
A useful classification of hypertension associated with cardio-
occurs with cyanide accumulation (Table 37.8). The metabolite
vascular surgery considers the clinical situation and time of
thiocyanate can accumulate with acute or chronic kidney in-
onset [32] (Table 37.7). Acute postoperative hypertension usu-
jury, and thiocyanate levels should be monitored. Thiocyanate
ally starts 2 to 6 hours after surgery and may persist for 24 to
is removed with dialysis. Nitroprusside is light sensitive and
48 hours. The immediate postoperative period (up to 2 hours)
must be wrapped in aluminum foil.
represents a time of significant patient instability, and BPs can
vary widely mediated by increased catecholamines [33]. The
goal is to avoid overshoot hypotension or TOD. Intravenous
Nitroglycerin
infusions or minibolus therapy allows the most controlled ap- Nitroglycerin preferentially dilates the venous system via cyclic
proach to BP regulation [34]. Nitroprusside or labetalol is ef- guanosine monophosphate. Left ventricular diastolic pressure
fective in most situations; nitroglycerin is also beneficial [31]. is reduced without any significant change in stroke volume or
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 37: Evaluation and Management of Hypertension in the Intensive Care Unit 379

TA B L E 3 7 . 8 flow. There is no dosage adjustment with renal failure, but


some adjustment may be needed with severe hepatic disease.
COMPLICATIONS OF TREATING HYPERTENSION Labetalol is a recommended agent with ischemic CVA or
aortic dissection and hypertension [19,24]. It has been used
Complication Causes with pheochromocytoma crisis because of its 1 -blocker prop-
erties and in aortic dissection because of its beta-blocker
Overshoot hypotension Infusion rate too rapid properties. The alpha-blocker effects of this agent can cause
Prolonged duration of effect orthostatic hypotension. The ratio of beta-blockade to alpha-
Additive drug effects blockade is approximately 7 to 1. Any contraindication to beta-
New cardiac disease blockers applies to labetalol.
Volume depletion
Worsening neurologic Cerebral ischemia secondary to
status low blood pressure Calcium Antagonists
Hypertensive encephalopathy
Increased intracranial pressure CCBs, particularly dihydropyridines, are widely used in the
Medication side effect ICU. Calcium antagonists have been used for hypertensive ur-
Thiocyanate toxicity gencies and emergencies and are given via the parenteral or
Metabolic abnormality enteral routes.
Worsening of hypertension Volume overload
Pseudotolerance
Dihydropyridines
Unsuspected secondary Nifedipine. It is administered orally, decreases peripheral vas-
hypertension cular resistance, and increases collateral coronary blood flow.
Poor medical regimen These effects result in decreased myocardial oxygen consump-
Poor compliance tion, despite a tendency to reflex tachycardia and increased
Metabolic acidosis Cyanide toxicity CO and stroke volume (in patients with preserved left ventricle
Tissue hypoperfusion secondary function). Sublingual nifedipine should be abandoned because
of safety concerns. The absorption is erratic; serious side ef-
Worsening renal function Hypoperfusion fects from prolonged hypotension have been described, and
Volume depletion the target BP is difficult to predict. Serious complications have
Acute tubular necrosis included myocardial infarction or ischemia, worsening renal
function, and cerebral ischemia [38].

Nicardipine. It is a rapid-acting systemic and coronary artery


CO, but MAP usually falls modestly. Nitroglycerin increases vasodilator. It has minimal effects on cardiac conduction and
flow via collateral coronary blood vessels and can improve contractile function. Its advantages include potency, rapid
epicardial coronary blood flow. Nitroglycerin is useful after onset, and ability to titrate in response to BP changes [39].
coronary bypass grafting, in coronary ischemia, and in heart Disadvantages include tachycardia, hypotension, nausea, and
failure. Nitroglycerin should be avoided in patients who have vomiting. There is minimal cardiac depression, and continuous
increased intracranial pressure, aortic stenosis, or hypertrophic administration requires continuous monitoring.
obstructive cardiomyopathy.
Nimodipine. It crosses the bloodbrain barrier and has
recently been recommended for neurological emergencies
Hydralazine [24,29]. A recent review of its use in SAH showed a statistically
Parenteral hydralazine was removed from the market in 1993 significant benefit on risk for severe disability, vegetative state,
and returned in 1994. It is a direct arterial vasodilator that or death, but its putative effect on preventing vasospasm is less
increases CO and heart rate. Metabolism is by hepatic acety- clear [28].
lation, the speed of which is genetically determined (slow vs.
rapid acetylators). Excretion is renal. It is effective for eclamp- Clevidipine. It is a parenteral, short-acting calcium antagonist
sia or left ventricular failure. Salt and water retention occur, with a rapid onset that is a potent arterial dilator with little ef-
requiring diuretics and beta-blockers in many cases. It is con- fect on venous capacitance or myocardial contraction. It may
traindicated with aortic dissection. also prevent sequelae of ischemic damage through antioxida-
tive properties [40].

Nondihydropyridines (Rate-Slowing
Beta-Blockers Calcium Channel Blockers)
Several beta-blockers, such as propranolol (nonselective), Verapamil. It is a phenylalkylamine CCB, which slows atri-
metoprolol (selective), and short-acting esmolol (selective), can oventricular conduction and has a pronounced negative in-
be given parenterally. Labetalol is the beta-blocker most com- otropic effect, with a rapid onset of action and a relatively
monly used in the ICU. low incidence of serious side effects. Verapamil can be given
Labetalol is a racemic mixture of a nonselective beta-blocker as repeated small boluses or a continuous intravenous infu-
and a selective 1 -antagonist, and may be administered as mini- sion. The disadvantages include induction of various degrees
bolus or infusion, allowing titration of effect, rapid onset, and of heart block and worsening heart failure because of its neg-
offset of action with prompt reduction in SVR and BP. The beta- ative inotropic effects.
blocker component prevents reflex tachycardia or significant
changes in CO. Myocardial oxygen consumption is reduced, Diltiazem. It is a benzothiazepine calcium antagonist available
and coronary hemodynamics are improved in patients with as an intravenous preparation. It has effects intermediate be-
CAD. Labetalol does not significantly affect cerebral blood tween verapamil and dihydropyridines. It is widely used to slow
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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380 Section III: Cardiovascular Problems and Coronary Care

the ventricular response to atrial fibrillation but not as a pri- TA B L E 3 7 . 9


mary antihypertensive agent.
SUMMARY OF RECOMMENDATIONS BASED ON
RANDOMIZED CONTROLLED TRIALS

Angiotensin Converting Enzyme Inhibitors The best choice of antihypertensive agent in hypertensive
urgency remains unclear [17]
Captopril The best choice of antihypertensive agent in a hypertensive
emergency remains unclear [17]
Captopril was the first ACE inhibitor available in the United There are no randomized trials comparing different
States. It is rapidly absorbed, with peak blood levels reached 30 treatment goals in hypertensive emergencies, but it is
minutes after oral administration. Unlike some ACE inhibitors, recommended that blood pressure not be lowered
captopril is not ingested as a prodrug and is therefore active as by more than 25% within the first hour and then to
soon as it is absorbed. It is particularly effective in patients with 160/100110 mm Hg within the next 26 h [6]
heart failure or recent myocardial infarction with depressed There is not enough evidence to evaluate the effect of
ejection fraction. There is a risk of acute hypotension or wors- altering blood pressure during acute stroke, though it is
ening renal function in patients who are volume depleted, have recommended to treat extremely elevated systolic
bilateral high-grade renal artery stenoses, or high-grade steno- (>220 mm Hg) or diastolic blood pressures (>120 mm Hg)
sis in a solitary functioning kidney. Other acute side effects in- [24]
clude bronchospasm, hyperkalemia, cough, angioedema, rash, There is not enough evidence to recommend specific blood
and dysgeusia. It can accumulate with renal failure. pressure management in acute intracerebral hemorrhage
though it is recommended to treat extremely elevated
systolic (>200 mm Hg) or diastolic blood pressures
Enalaprilat (>150 mm Hg) [29]
Enalaprilat is the only ACE inhibitor that can be administered
parenterally. It is the active form of the oral agent, enalapril. A
limited-dose titration response restricts the use of enalaprilat
to lesser elevations in BP. Intravenous ACE inhibitor therapy
is contraindicated in acute heart failure or acute myocardial Fenoldopam
infarction complicated by left ventricular dysfunction.
Fenoldopam is a specific dopamine I receptor agonist that is
free of - and -adrenergic receptor effects. It reduces SVR,
increases renal blood flow, increases fractional excretion of
-Agonists sodium, and increases water clearance. It is metabolized in the
liver to multiple metabolites with uncertain clinical activity and
may be particularly effective with impaired renal function, al-
Clonidine though a recent randomized controlled trial showed no differ-
Clonidine is a central 2 -agonist that decreases peripheral vas- ence compared to dopamine in renal protection [41].
cular resistance, venous return, and heart rate, and can con- Disadvantages are related to vasodilation, including flush-
tribute to reduction in CO. Clonidine is available orally and ing, headache, hypotension, nausea, and occasional ECG
as a transdermal patch with an effectiveness of approximately changes.
1 week. The patch should not be used to initiate therapy in
the ICU, because it takes several days to achieve a steady state.
However, patients previously on clonidine who are unable to Diuretics
take oral medications may be converted to a patch. Clonidine
has been administered in an oral titration regimen to achieve Many patients are actually hypovolemic from pressure natri-
gradual BP control in a period of 2 to 3 hours. Major dis- uresis [5]. Patients with postoperative hypertension, cardiac
advantages are sedation, dry mouth, and orthostatic hypoten- dysfunction, or evidence of pulmonary edema may require di-
sion. Caution should be used in patients requiring monitoring uresis. Many parenteral antihypertensive agents can cause fluid
of mental status. Rebound hypertension may be observed if it retention. Loop diuretics can help control intravascular vol-
is abruptly discontinued, particularly at higher doses. ume, maintain urine output, and prevent resistance to antihy-
pertensive therapy. They are given as a bolus or a slow infusion
and have a threshold effect. Responseincreased diuresis and
natriuresisis not seen unless sufficient drug reaches the renal
-Adrenergic Inhibitors tubules. Doses are titrated until increased urine output is seen
or maximum doses are reached when other therapy must be
Phentolamine initiated.
Several -adrenergic inhibitors are available for oral adminis-
tration. The only available intravenous agent with -adrenergic
blocking properties is phentolamine, a nonselective -receptor CONCLUSIONS
blocking agent. Its use is reserved for states associated with
excess catecholamine levels, such as pheochromocytoma, re- Advances in evaluation and management of hypertension in the
bound hypertension, or drug ingestion. The hypotensive effect ICU, based on randomized controlled trials or meta-analyses
of a single intravenous bolus lasts less than 15 minutes and is of such trials, are summarized in Table 37.9. Given the scarcity
associated with significant reflex tachycardia. The advantage of of data to support one particular hypertensive agent above an-
phentolamine is its specific effect with pheochromocytoma. It is other, the choice and goals of therapy are largely based on
part of the anesthetic regimen in perioperative control of these consensus recommendations and should be guided by the sus-
patients. Disadvantages include abdominal cramping and pain, pected etiology of the hypertension, the extent of TOD, and
vomiting, diarrhea, tachycardia, dizziness, and arrhythmias. the individual hemodynamic profile of the patient.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 37: Evaluation and Management of Hypertension in the Intensive Care Unit 381

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report of the American College of Cardiology Foundation/American Heart ine and sodium nitroprusside in the immediate treatment of severe hyperten-
Association Task Force on Practice Guidelines: developed in collaboration sion. Am J Hypertens 7:623628, 1994.
with the International Society for Heart and Lung Transplantation. Circula- 40. Aronson S, Dyke CM, Stierer KA, et al: The ECLIPSE trials: comparative
tion 119:19772016, 2009. studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine
21. Mancia G, De Backer G, Dominiczak A, et al: 2007 guidelines for the man- for acute hypertension treatment in cardiac surgery patients. Anesth Analg
agement of arterial hypertension: the Task Force for the Management of 107:11101121, 2008.
Arterial Hypertension of the European Society of Hypertension (ESH) and 41. Bove T, Landoni G, Calabro MG, et al: Renoprotective action of fenoldopam
of the European Society of Cardiology (ESC). Eur Heart J 28:14621536, in high-risk patients undergoing cardiac surgery: a prospective, double-blind,
2007. randomized clinical trial. Circulation 111:32303235, 2005.
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382 Section III: Cardiovascular Problems and Coronary Care

CHAPTER 38 UNSTABLE ANGINA/


NONST-SEGMENT ELEVATION
MYOCARDIAL INFARCTION
SUZANNE J. BARON, CHRISTOPHER P. CANNON AND MARC S. SABATINE

The spectrum of acute coronary syndromes (ACS) ranges from arteritis; and (e) conditions leading to increased myocardial
unstable angina (UA) to nonST-segment elevation myocardial oxygen demand, such as anemia, sepsis, or hypoxia [9]. Indi-
infarction (NSTEMI) to ST-segment elevation myocardial in- vidual patients may have several of these processes contribute
farction (STEMI) [1]. The latter condition is usually caused by to the onset of their UA/NSTEMI.
acute total obstruction of a coronary artery [2,3], and urgent
reperfusion is the mainstay of therapy. In contrast, the nonST-
segment elevation acute coronary syndromes (NSTEACS)UA Plaque Rupture
and NSTEMIare usually associated with a severe, although
nonocclusive, lesion in the culprit coronary artery [4]. Atherosclerosis is a silent process that usually begins 20 to 30
Every year in the United States, approximately 1.3 million years prior to a patients clinical presentation [10,11]. Plaque
patients are admitted to the hospital with ACS; about 900,000 rupture can be precipitated by multiple factors, including en-
of these patients are suffering from UA/NSTEMI as compared dothelial dysfunction [12], plaque lipid content [13], local in-
with approximately 400,000 patients suffering from STEMI flammation [14], coronary artery tone at the site of irregular
[5,6]. Worldwide, these numbers are each several times the plaques and local shear stress forces, platelet function [15,16],
totals in the United States. In the past few years, numerous and the status of the coagulation system (i.e., a potentially pro-
advances have been made in the understanding of the patho- thrombotic state) [17,18]. These processes culminate in forma-
physiology, diagnosis, risk stratification, and management of tion of platelet-rich thrombi at the site of the plaque rupture
UA/NSTEMI. or erosion and the resultant ACS [1921].

DEFINITION Thrombosis
The definition of UA is largely based on the clinical presen- Coronary artery thrombosis plays a central role in the patho-
tation. Angina pectoris is characterized by a poorly localized genesis of UA/NSTEMI [4,19,20,2226], as demonstrated in
chest or arm discomfort or pressure (rarely described by pa- the Thrombolysis in Myocardial Infarction (TIMI) IIIA trial,
tients as pain) that is typically and reproducibly associated in which 35% of patients had definite thrombus and an ad-
with physical exertion or emotional stress, and relieved by rest ditional 40% had possible thrombus [4]. Thrombosis occurs
or sublingual nitroglycerin. UA is defined as angina pectoris in two interrelated stages: (a) primary hemostasis and (b) sec-
(or equivalent type of ischemic discomfort) with one of three ondary hemostasis [27,28]. The first stage of hemostasis is ini-
features: (a) occurring at rest (or with minimal exertion), usu- tiated by platelets as they adhere to damaged vessels and form
ally lasting more than 20 minutes; (b) being severe and of new a platelet plug. With rupture or ulceration of an atherosclerotic
onset (i.e., within 1 month); or (c) occurring with a crescendo plaque, the subendothelial matrix (e.g., collagen and tissue fac-
pattern (i.e., more severe, prolonged, or frequent) [7]. Some tor) is exposed to the circulating blood. Platelets then adhere
patients with this pattern of ischemic pain develop evidence of to the subendothelial matrix via the glycoprotein (GP) Ib re-
myocardial necrosis on the basis of serum biomarkers in the ceptor and von Willebrands factor (platelet adhesion). After
absence of ST-segment elevations on electrocardiogram (ECG) adhering to the subendothelial matrix, the platelet undergoes a
and thus have a diagnosis of NSTEMI. Previously, this diagno- conformational change from a smooth discoid shape to a spicu-
sis has been based on elevation of the creatine kinase (CK)-MB, lated form, which increases the surface area on which thrombin
but elevations in cardiac troponin T or I greater than the 99th generation can occur. This leads to degranulation of the alpha-
percentile of the upper limit of normal now define MI on the and dense granules and the subsequent release of thrombox-
basis of their higher sensitivity and specificity for myocardial ane A2, adenosine diphosphate (ADP), serotonin, and other
necrosis and powerful prognostic capability [8]. platelet aggregatory and chemoattractant factors, as well as
the expression and activation of GP IIb/IIIa receptors on the
platelet surface such that it can bind fibrinogen. This process is
PATHOPHYSIOLOGY called platelet activation. The final step is platelet aggregation,
that is, the formation of the platelet plug. Fibrinogen (or von
The development of UA/NSTEMI is due either to a reduction Willebrands factor) binds to the activated GP IIb/IIIa receptors
in the supply of blood flow and oxygen, or to an increase in my- of two platelets, thereby creating a growing platelet aggregate.
ocardial oxygen demand, or both. The five broad etiologies are Antiplatelet therapy has been directed at decreasing the forma-
(a) plaque rupture with superimposed nonocclusive thrombus; tion of thromboxane A2 (aspirin), inhibiting the ADP pathway
(b) dynamic obstruction (i.e., coronary spasm); (c) progressive of platelet activation (thienopyridines), and directly inhibiting
mechanical obstruction (i.e., restenosis); (d) inflammation and platelet aggregation (GP IIb/IIIa inhibitors; Fig. 38.1).
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Chapter 38: Unstable Angina/NonST-Segment Elevation Myocardial Infarction 383

FIGURE 38.1. Primary hemostasisprocess of


platelet adhesion, activation, and aggregation.
Platelets initiate thrombosis at the site of a ruptured
plaque: the first step is platelet adhesion (A) via the
glycoprotein (GP) Ib receptor in conjunction with
von Willebrands factor. This is followed by platelet
activation (B), which leads to a shape change in
the platelet, degranulation of the alpha and dense
granules, and expression of GP IIb/IIIa receptors on
the platelet surface with activation of the receptor,
such that it can bind fibrinogen. The final step is
Aspirin, platelet aggregation (C), in which fibrinogen (or
Thienopyridines von Willebrands factor) binds to the activated GP
IIb/IIIa receptors of two platelets. Aspirin (ASA)
and clopidogrel act to decrease platelet activation
(see text for details), whereas the GP IIb/IIIa in-
hibitors inhibit the final step of platelet aggregation.
[Adapted from Cannon CP, Braunwald E: Unstable
angina, in Braunwald E, Zipes DP, Libby P (eds):
Heart Disease: A Textbook of Cardiovascular
Medicine. 6th ed. Philadelphia, WB Saunders, 2001,
pp 12321263, with permission.]

and (c) it activates factor XIII, which leads to cross-linking and


Secondary Hemostasis stabilization of the fibrin clot [27].
Simultaneous with the formation of the platelet plug, the
plasma coagulation system is activated (Fig. 38.2). Follow-
ing plaque rupture, the injured endothelial cells on the vessel Coronary Vasoconstriction
wall become activated and release protein disulfide isomerase,
which acts to cause a conformational change in circulating tis- Another etiologic factor in UA/NSTEMI is dynamic obstruc-
sue factor [2932]. Tissue factor can then bind to factor VIIa tion, that is, coronary vasoconstriction. The process is identi-
and form a protein complex, leading to the activation of factor fied in three settings: (a) vasospasm in the absence of obstruc-
X. With the activation of factor X (to factor Xa), thrombin is tive plaque, (b) vasoconstriction in the setting of atherosclerotic
generated and acts to cleave fibrinogen to form fibrin. Throm- plaque, and (c) microcirculatory angina. Vasospasm can occur
bin plays a central role in arterial thrombosis: (a) it converts in patients without coronary atherosclerosis or in those with
fibrinogen to fibrin in the final common pathway for clot for- a nonobstructive atheromatous plaque. Vasospastic angina ap-
mation; (b) it is a powerful stimulus for platelet aggregation; pears to be due to hypercontractility of vascular smooth muscle
and endothelial dysfunction occurring in the region of spasm.
Prinzmetals variant angina, with intense focal spasm of a seg-
ment of an epicardial coronary artery, is the prototypic exam-
TF/VIIa ple [33]. Such patients have rest pain accompanied by transient
ST-segment elevation. Vasoconstriction more commonly occurs
in the setting of significant coronary atherosclerotic plaque,
Fondaparinux especially those with superimposed thrombus. Vasoconstric-
LMWH tion can occur as the result of local vasoconstrictors released
UFH from platelets, such as serotonin and thromboxane A2 [3436].
Vasoconstriction can also result from a dysfunctional coronary
X endothelium, which has reduced production of nitric oxide and
increased release of endothelin. Adrenergic stimuli, cold im-
mersion [37], cocaine [38,39], or mental stress [40] can also
Xa cause coronary vasoconstriction in susceptible vessels. A third
setting in which vasoconstriction is identified is microcircula-
tory angina (syndrome X). In this condition, ischemia results
from constriction of the small intramural coronary resistance
V, Ca ++ vessels [41]. Although no epicardial coronary artery stenoses
are present, coronary flow is usually slowed and does not in-
LMWH crease appropriately in response to a variety of signals.
Prothrombin Thrombin UFH
Bivalirudin

Progressive Mechanical Obstruction


Clopidogrel Aspirin
PLATELET Another etiology of UA/NSTEMI results from progressive lu-
minal narrowing. This is most commonly seen in the setting of
restenosis following percutaneous coronary intervention (PCI).
However, angiographic [42] and atherectomy studies [43,44]
GP IIb/IIIa Inhibitor have demonstrated that many patients without previous PCI
show progressive luminal narrowing of the culprit vessel, likely
FIGURE 38.2. Diagram of the major components of the clotting cas- related to rapid cellular proliferation, in the period preceding
cade and the areas targeted by antithrombotic agents. the onset of UA/NSTEMI.
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384 Section III: Cardiovascular Problems and Coronary Care

TA B L E 3 8 . 1
BRAUNWALD CLINICAL CLASSIFICATION OF UNSTABLE ANGINA

Death or myocardial
Class Definition infarction to 1 ya (%)

Severity
Class I New onset of severe angina or accelerated angina; no rest pain 7.3
Class II Angina at rest within past month but not within preceding 48 h (angina at 10.3
rest, subacute)
Class III Angina at rest within preceding 48 h (angina at rest, subacute) 10.8b
Clinical circumstances
A (secondary angina) Develops in the presence of an extracardiac condition that intensifies 14.1
myocardial ischemia
B (primary angina) Develops in the absence of an extracardiac condition 8.5
C (postinfarction angina) Develops within 2 wk after acute myocardial infarction 18.5c
Intensity of treatment Patients with unstable angina can also be divided into three groups
depending on whether unstable angina occurs: (a) in the absence of
treatment for chronic stable angina, (b) during treatment for chronic
stable angina, or (c) despite maximal anti-ischemic drug therapy. These
three groups can be designated subscripts 1, 2, or 3, respectively
Electrocardiographic changes Patients with unstable angina can be further divided into those with or
without transient ST-Twave changes during pain
a
Data from Scirica BM, Cannon CP, McCabe CH, et al: Prognosis in the thrombolysis in myocardial ischemia III registry according to the Braunwald
unstable angina pectoris classification. Am J Cardiol 90(8):821, 2002.
b
p = 0.057.
c
p < 0.001.
Reprinted from Braunwald E: Unstable angina: a classification. Circulation 80:410, 1989, with permission.

Secondary Unstable Angina Electrocardiogram


Secondary UA is defined as UA precipitated by conditions ex- The ECG is the most widely used tool in the evaluation of is-
trinsic to the coronary arteries in patients with prior coronary chemic heart disease. In UA/NSTEMI, ST-segment depression
stenosis and chronic stable angina. This change could occur ei- (or transient ST-segment elevation) and T-wave changes occur
ther as a result of an increase in myocardial oxygen demand or in up to 50% of patients [4749]. Two analyses have shown
as a decrease in coronary blood flow. Conditions that increase ST-segment deviation even of only 0.5 mm to be a specific and
myocardial demand include tachycardia (e.g., a supraventricu- important measure of ischemia and prognosis (see later in the
lar tachycardia or new-onset atrial fibrillation with rapid ven- chapter) [47,50]. T-wave changes are generally considered less
tricular response), fever, thyrotoxicosis, hyperadrenergic states, specific than ST-segment changes and the presence of T-wave
and elevations of left ventricular (LV) afterload, such as hyper- inversions of only 1 mm in patients with acute ischemic syn-
tension or aortic stenosis. Secondary UA can also occur as a re- dromes may add little to the clinical history. T-wave inversions
sult of impaired oxygen delivery, as in anemia, hypoxemia (e.g., of greater than or equal to 3 mm are considered significant
due to pneumonia or congestive heart failure), hyperviscosity [47,50].
states, or hypotension. Although one might expect secondary
angina to be associated with a more favorable prognosis, it ap-
pears to have a worse prognosis than primary UA [45] (Table
38.1), likely due to serious patient comorbidities. Cardiac Biomarkers
UA is not associated with any detectable damage to the my-
ocyte. The diagnosis of NSTEMI is made if there is biochemical
CLINICAL PRESENTATION evidence of myocardial necrosis, that is, a positive cardiac tro-
ponin T or I or CK-MB. The cut point for definition of an MI
AND DIAGNOSIS is elevation in troponin T or I greater than the 99th percentile
of the upper reference range [8]. Although false-positive tro-
History and Physical Examination ponin elevations do occur [51], elevations in cardiac biomark-
ers in the absence of other clinical data consistent with an ACS
A description of ischemic pain is the hallmark of UA/ usually do represent true myocardial damage. In these cases,
NSTEMI. Ischemic chest pain is usually described as a discom- myocyte damage is due to etiologies besides atherosclerotic
fort or pressure (rarely as a pain) that is brought on by exertion coronary artery disease, such as myocarditis, LV strain from
and relieved by rest. It is generally located in the retrosternal re- congestive heart failure, hypertensive crisis, or right ventricu-
gion but sometimes in the epigastrium and frequently radiates lar strain from pulmonary embolus [52].
to the anterior neck, left shoulder, and left arm. The physical Unfortunately, the limitation of standard troponin assays
examination may be unremarkable or may support the diag- is that they tend to have a low sensitivity in the first few
nosis of cardiac ischemia [46]. Signs that suggest ischemia are hours of symptom onset and become positive only usually 6 to
sweatiness, pale cool skin, sinus tachycardia, a fourth heart 12 hours after symptom onset. However, the recent devel-
sound, and basilar rales on lung examination. opment of high-sensitivity troponin assays has significantly
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Chapter 38: Unstable Angina/NonST-Segment Elevation Myocardial Infarction 385

improved the sensitivity of this test. Two recent studies have comes. Moreover, data from several trials have demonstrated
found that the use of high-sensitivity assays improve the early that early risk assessment (especially using troponins) has also
diagnosis of MI with sensitivity now exceeding 90% when been useful in predicting which patients will derive the great-
tested in patients with chest pain at the time of presentation est benefit from newer and more potent antithrombotic thera-
to the hospital [53,54]. Moreover, high-sensitivity assays can pies, such as low-molecular-weight heparin (LMWH) and GP
detect elevated levels of troponin in approximately 10% of out- IIb/IIIa inhibitors. Risk assessment can similarly be used to
patients with stable coronary disease, and these individuals are determine the most appropriate level of care and monitoring
at a higher risk of subsequent cardiovascular death [55]. (i.e., between the coronary intensive care unit or the step-
Ultrasensitive troponin assays, which have limits of detec- down/telemetry unit). The management strategy refers to
tion lesser than the levels seen in a normal reference population, whether early angiography is performed with revascularization
are also being developed. In a study looking at patients with as appropriate directly following the index event or whether a
NSTEACS, 72% of patients with NSTEMI were found to have conservative or ischemia-driven strategy is carried out, with
circulating troponin levels at baseline greater than the 99th per- noninvasive assessment of residual ischemia, and angiography
centile (nano-cTnI >0.003 g/L) when ultrasensitive troponin and revascularization performed only if recurrent ischemia is
assays were utilized; yet all of these patients had an initially documented (see later in the chapter).
negative current-generation troponin assay. When these assays
were used in patients presenting with UA (defined as lack of
elevation of troponin using a current-generation commercial
assay), 44% of patients had circulating troponin levels greater Risk Assessment Using Clinical Predictors
than the 99th percentile and 8 hours later, the percentage had
The initial clinical evaluation can be used to risk-stratify pa-
risen to 82% [56]. Similarly, ultrasensitive assays have been
tients quickly and assist in the triage [67,68]. As described in
used to detect rises in circulating troponin in proportion to the
the ACC/AHA UA/NSTEMI guideline (Table 38.2), high-risk
amount of ischemia experienced during exercise stress testing
patients can be identified by the presence of prolonged, ongo-
[57]. Thus, in the future, troponin may move from a semiquan-
ing pain at rest, ST-segment depression of greater than or equal
titative assay (negative in most individuals and quantified in
to 0.1 mV, positive troponin value, or the presence of hypoten-
a subset) to quantifiable in all patients. The clinical implications
sion or congestive heart failure on physical examination [67].
of very low level values reported from ultrasensitive assays will
Such patients should be considered for the coronary care unit
need to be defined.
although the cardiac step-down (telemetry) unit may be ade-
quate depending on the clinical situation. Lower risk patients
can be adequately monitored and managed in a step-down unit.
Cardiac Imaging
Currently, cardiac imaging is assuming increasing importance
in the early diagnosis of patients presenting with suspected Individual High-Risk Subgroups
UA/NSTEMI, especially when the ECG is normal, nonspe-
cific, or obscured by left bundle branch block or a paced Trials have identified several clinical subgroups that are at
rhythm. Myocardial perfusion imaging using technetium ses- higher risk of adverse outcomes when they present with
tamibi has been useful for patients presenting with chest pain UA/NSTEMI. These groups derive greater benefit from more
in the emergency department without a diagnostic ECG or pos- aggressive therapy.
itive biomarkers to discriminate patients with coronary artery
disease from those with noncardiac chest pain [58,59]. Simi- Elderly Patients
larly, echocardiography is useful to screen for regional or global
LV dysfunction, which may help in establishing (or excluding) Elderly patients comprise a subgroup for which outcomes
the diagnosis of ischemic heart disease in patients who present are always worse compared with younger patients. In
to the emergency department with chest pain [60]. Coronary UA/NSTEMI, elderly patients appear to derive greater bene-
computed tomography angiogram (CTA) has also been shown fit from the newer, more potent antithrombotic therapies. In
to be effective in excluding coronary artery disease in patients the Efficacy and Safety of Subcutaneous Enoxaparin in Non-
presenting to the emergency department with a low-risk story Q-Wave Coronary Events (ESSENCE) trial, enoxaparin had
of chest pain, nondiagnostic ECG, and negative biomarkers greater benefit in patients 65 years or older as compared with
[61]. All of these modalities can also assess LV function, a younger patients [69]; a similar finding was noted in the TIMI
powerful determinant of subsequent prognosis after MI (and 11B trial [70]. For the GP IIb/IIIa inhibitors, an equivalent rel-
presumably after UA) [6264]. Coronary angiography is also ative benefit was observed in older versus younger patients,
used to establish the diagnosis of ACS and is considered the although the absolute benefit in number of events prevented
gold-standard modality to define the extent of coronary dis- is higher in elderly patients because they have higher base-
ease, and as a prelude to percutaneous revascularization (see line risk [49,71,72]. However, this increase in absolute benefit
later in the chapter) [4,48,65,66]. comes with the added price of an increased incidence of bleed-
ing with GP IIb/IIIa inhibitors in elderly patients [71,72]. With
regard to an invasive versus conservative management strat-
egy, patients 65 years or older have better outcomes at 1 year
RISK STRATIFICATION when managed with an invasive strategy (12.5% vs. 19.5%;
p = 0.03; age interaction p = 0.04) [73]. Similarly, in Frag-
Given the multitude of treatment options for patients with min and Fast Revascularization during Instability in Coronary
UA/NSTEMI, risk stratification currently refers to two simulta- Artery Disease (FRISC) II, and Treat Angina with Aggrastat
neous processes (frequently carried out at the time of hospital and Determine Cost of Therapy with an Invasive or Conserva-
presentation): (a) risk assessment (i.e., prediction of mortal- tive Strategy (TACTICS)-TIMI 18, there was a greater absolute
ity/morbidity risk), and (b) selection of a management strategy benefit of an early invasive strategy in patients 65 years and
(i.e., an early invasive vs. early conservative approach). older [74,75]. Thus, in UA/NSTEMI, elderly patients are at
Risk assessment, using clinical and laboratory markers, higher risk and derive particular benefit from more aggressive
identifies which patients are at highest risk for adverse out- antithrombotic and interventional therapy.
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386 Section III: Cardiovascular Problems and Coronary Care

TA B L E 3 8 . 2
CLINICAL FEATURES ASSOCIATED WITH HIGHER LIKELIHOOD OF CORONARY ARTERY DISEASE AMONG
PATIENTS PRESENTING WITH SYMPTOMS SUGGESTIVE OF UNSTABLE ANGINA

Intermediate likelihood Low likelihood (no high- or


(no high-likelihood features, intermediate-likelihood features,
Feature High likelihood (any below) but any below) but may have any below)

History History of crescendo symptoms Prior history of CAD, PAD, or


in prior 48 h CVA
Prior aspirin use
Character of pain Ischemic chest pain that is Ischemic, prolonged chest pain Atypical chest pain not
prolonged (>20 min), that is now resolved consistent with cardiac chest
ongoing, and occurring at rest pain
Nocturnal angina
Examination Age >75 y Age >70 y
Signs of CHF (pulmonary edema
on CXR; rales and/or S3 on
examination)
Hypotension
New or worsening MR murmur
ECG Angina at rest with transient T-wave changes Normal ECG
ST-segment changes >0.5 mm
Sustained VT Pathological Q-waves
Resting ST-segment depressions
<1 mm
Cardiac markers Positive Normal Normal

CAD, coronary artery disease; CHF, congestive heart failure; CVA, cardiovascular accident; CXR, chest X-ray; DM, diabetes mellitus; ECG,
electrocardiogram; MR, mitral regurgitation; PAD, peripheral arterial disease; VT, ventricular tachycardia.
Adapted from Anderson JL, Adams CD, Antman EM, et al: ACC/AHA 2007 guidelines for the management of patients with unstable
angina/non-ST-segment elevation myocardial infarction-2002: executive summary: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for Management of Patients With Unstable
Angina/Non-ST-Segment Elevation Myocardial Infarction). Circulation 116:803877, 2007.

Gender Differences 1 year as well (hazard ratio [HR] 1.65; 95% confidence interval
[CI] 1.3 to 2.1) [81].
A patients gender may factor into the decision regarding
Given the high risk of adverse cardiovascular outcomes as-
which treatment strategy to pursue in patients presenting with
sociated with diabetes, researchers have looked to see if certain
UA/NSTEMI. Subgroup analyses from some trials, including
treatment strategies may be of more benefit in this particular
FRISC II [76], Randomized Intervention Treatment of Angina
subgroup. The relative benefit of early GP IIb/IIIa inhibition
(RITA) 3 [77], and Organization to Assess Strategies for Is-
has been found to be significantly higher in patients with di-
chemic Syndromes (OASIS) 5 [78], suggested that an early in-
abetes, with a 70% relative reduction in events ( p = 0.002)
vasive strategy may be associated with a higher risk of death or
[82], as compared with a 30% reduction in the overall popula-
MI in women, whereas other studies demonstrated that an early
tion. More recently, a meta-analysis of all placebo-controlled,
invasive strategy resulted in improved outcomes in women as
IIb/IIIa inhibitor trials found a mortality benefit of early IIb/IIIa
well as men [79]. Because subgroup analyses may be insuffi-
inhibition in patients with diabetes, with no mortality differ-
ciently powered to address this question, a meta-analysis was
ence in those without nondiabetes [83]. For an invasive versus
performed using the data of eight large-scale trials. This meta-
conservative strategy, the relative benefit in patients with dia-
analysis demonstrated that high-risk women (classified as pa-
betes of an early invasive strategy was similar to that of those
tients with positive biomarkers on presentation) had a 33%
without diabetes, but the absolute benefit was higher among
lower odds of death, MI or rehospitalization with ACS (OR
those with diabetes [84]. Similarly in the Trial to Assess Im-
0.67) with an invasive strategy, whereas low-risk women (pa-
provement in Therapeutic Outcomes by Optimizing Platelet
tients with normal biomarkers on presentation) did not have
Inhibition with Prasugrel - Thrombolysis in Myocardial In-
a significant benefit with invasive treatment [80]. These find-
farction (TRITON-TIMI) 38 trial, patients with diabetes had
ings are reflected in the 2007 AHA/ACC guidelines for the
a 40% reduction in MI (8.2% vs. 13.2%; p < 0.001) with
management of patients with UA/NSTEMI, which recommend
the use of more intensive antiplatelet therapy with prasugrel
that women with high-risk features be considered for invasive
when compared to clopidogrel. Those without diabetes saw
treatment, whereas women with low-risk features be treated
only an 18% reduction in MI with prasugrel (7.2% vs. 8.7%;
conservatively [67].
p = 0.009) [85]. Thus, patients with diabetes represent a high-
risk group that deserves aggressive pharmacologic and revas-
Patients with Diabetes cularization treatments.
Patients with diabetes have long been known to be at higher risk
than those without diabetes for adverse outcomes with ACS. In
a large-scale meta-analysis, patients with diabetes were found Risk Assessment by Electrocardiography
to have a significantly higher mortality at 30 days (2.1% vs.
1.1%; p < 0.001). Furthermore, having diabetes at presenta- The admission ECG is very useful in predicting long-term
tion with an NSTEMI was associated with a higher mortality at adverse outcomes. In the TIMI III registry of patients with
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Chapter 38: Unstable Angina/NonST-Segment Elevation Myocardial Infarction 387

UA/NSTEMI, multivariable predictors of 1-year death or MI The presence of elevated biomarkers also correlates with
included left bundle branch block and ST-segment deviation the utility of particular therapies. In a trial examining the ben-
of 0.5 mm or greater [47]. The presence of only 0.5-mm efit of abciximab in patients with NSTEMI, the reduction in
ST-segment depression on the admission ECG has also been death or MI at 6 months was 70% in those who were troponin
found to be an independent determinant of 4-year survival T positive, whereas there was no significant benefit for those
[50]. In contrast, the presence of T-wave changes was asso- who were troponin T negative ( p < 0.001) [98] (Fig. 38.4, left).
ciated with only a modest [50] or no increase in subsequent These findings have been duplicated with tirofiban versus hep-
death or MI risk compared with no ECG changes [47]. Simi- arin in the Platelet Receptor Inhibition for Ischemic Syndrome
lar findings were observed in predicting 30-day and 6-month Management (PRISM) (Fig. 38.4, right) and PRISM in Patients
outcomes in the Global Use of Strategies to Open Occluded Limited by Unstable Signs and Symptoms (PRISM-PLUS) tri-
Coronary Arteries (GUSTO) IIb study, with the presence of als [99,100] and more recently in the Intracoronary Stenting
ST-segment deviation of greater than 0.5 mm conferring a and Antithrombotic Regimen-Rapid Early Action for Coro-
higher mortality than T-wave changes [86]. nary Treatment 2 (ISAR-REACT 2) trials [96]. In the TIMI
With regard to relative treatment benefit of particular ther- 11B trial, even when looking at patients who were CK-MB
apies, in the ESSENCE trial, patients with ST-segment devi- negative, those who were troponin I positive derived a signif-
ation treated with enoxaparin had a significant reduction in icantly greater benefit from the enoxaparin versus UFH, com-
cardiac events compared with patients treated with unfraction- pared with those who had both markers negative [101]. Re-
ated heparin (UFH; odds ratio [OR] 0:60; p < 0.01), whereas search has also demonstrated that biomarkers are useful when
those without ST-segment deviation did not [87]. Similar find- choosing an invasive versus conservative strategy in patients
ings were observed in the TIMI 11B trial [70]. In both the with UA/NSTEMI. In both the FRISC II and TACTICS-TIMI
FRISC II and TACTICS-TIMI 18 trials, an invasive strategy 18 trials, patients who had a positive troponin T or I (includ-
had a particular benefit in patients with ST-segment depression ing those who had very low levels of troponin) had a dramatic
at presentation [84,88]. Thus, not only ST-segment deviation reduction in cardiac events after allocation to an invasive strat-
is a marker of increased risk of adverse outcomes, but it also egy [91,102]. Thus, there is now evidence from multiple trials
indicates those patients who may derive greater benefit from that the use of troponins can assist in both assessing the risk
aggressive antithrombotic and interventional therapy. and determining which patients should be treated with newer
antithrombotic agents and an invasive management strategy.

Risk Assessment by Cardiac Markers Other Biomarkers


Patients with an elevated C-reactive protein (CRP) have an
Creatine Kinase-MB and the Troponins increased risk of death and adverse cardiovascular events
Patients with NSTEMI have a worse long-term prognosis than [103,104]. Even among patients with negative troponin I at
those with UA [73,89]. It has now been shown that patients baseline, CRP is able to discriminate high- and low-risk groups
with elevated troponins, even if their CK-MB is normal, also [105]. Recently, CRP levels have been shown to significantly
have a significantly worse prognosis, with a higher risk of sub- add to low-density lipoprotein (LDL) levels in predicting recur-
sequent cardiac complications, including mortality [9092]. rent adverse cardiovascular events in patients post-ACS [106].
Beyond just a positive versus negative test result, there is a B-type natriuretic peptide (BNP) as well as N-terminal probrain
linear relationship between the level of troponin T or I in the natriuretic peptide (NT-proBNP), both biomarkers of LV wall
blood and subsequent risk of death: the higher the troponin, stress, have also been shown to be a powerful predictor of
the higher the mortality risk (Fig. 38.3). Furthermore, elevated mortality and heart failure in patients with NSTEMIs [107
markers (both troponin T and CK-MB) have been shown to 110]. More recently, studies involving growth-differentiation
correlate with a higher rate of thrombus at angiography [4,93 factor 15 (GDF-15), a molecule that is induced by inflammation
96]. Thus, cardiac biomarkers are very useful not only in di- and cellular injury, have shown this molecule to be a similarly
agnosing infarction [97] but also in assessing risk for patients powerful predictor of adverse cardiovascular outcomes after
who present with acute UA/NSTEMI. NSTEMI [111]. Researchers have even suggested that GDF-15
may be able to direct treatment strategies after NSTEMI. A
retrospective study looking at GDF-15 levels in patients with
NSTEMI found that patients with markedly elevated GDF-15
levels had lower mortality when an invasive treatment strat-
egy was used as opposed to conservative management [112].
p
Larger prospective studies are needed to see if GDF-15 will be a
useful tool when deciding on the management of patients with
NSTEMI. Multimarker strategies have also been employed to
improve risk stratification. When using CRP and troponin T
together, mortality is 0.4% for patients with both markers neg-
ative, 4.7% if either CRP or troponins are positive, and 9.1%
if both are positive [105]. Similarly, the combination of tro-
ponin, CRP, and BNP can predict up to a 13-fold gradient in
mortality post-ACS [113]. It should be noted that although
CRP and BNP can be used as prognostic indicators, only tro-
ponin and potentially GDF-15 can identify patients who may
L derive greater benefit from specific interventions.

FIGURE 38.3. TIMI IIIB: a direct relationship was observed between


increasing levels of troponin I and a higher 42-day mortality. cTnI, Combined Risk Assessment Scores
cardiac specific troponin I; Ng, negative. [Adapted from Antman EM,
Tanasijevic MJ, Thompson B, et al: Cardiac-specific troponin I levels to The TIMI risk score uses clinical factors, the ECG, and cardiac
predict the risk of mortality in patients with acute coronary syndromes. markers. It was developed using multivariate analysis, which
N Engl J Med 335:13421349, 1996, with permission.] identified seven risk factors: age 65 years or older, more than
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388 Section III: Cardiovascular Problems and Coronary Care

CAPTURE PRISM
Heparin Abciximab + heparin Heparin Tirofiban + heparin

19.6 p < 0.001 p < 0.001


Death or MI at 30 days (%)

Death or MI at 30 days (%)


12.2

4.9 5.2 5.8


5.0 5.7 3.8

FIGURE 38.4. Use of troponin to determine benefit of GP IIb/IIIa inhibition. Benefit of abciximab in
the CAPTURE trial of patients with refractory unstable angina treated with angioplasty in those with
positive versus negative troponin T at study entry (left panel). Greater benefit of tirofiban versus heparin
in patients with UA/NSTEMI was also seen in patients with positive troponin I values in the PRISM
trial, with a nearly 70% reduction in death or MI at 30 days with the IIb/IIIa inhibitor (right panel).
[Data from Hamm CW, Heeschen C, Goldmann B, et al: Benefit of abciximab in patients with refractory
unstable angina in relation to serum troponin T levels. N Engl J Med 340(21):16231629, 1999; and
Heeschen C, Hamm CW, Goldmann B, et al: Troponin concentrations for stratification of patients with
acute coronary syndromes in relation to therapeutic efficacy of tirofiban. Lancet 354(9192):17571762,
1999, with permission.]

three risk factors for coronary artery disease, documented coro- lesion, treatment of residual ischemia, and long-term secondary
nary artery disease at catheterization, ST-segment deviation of prevention. Antithrombotic therapy (e.g., aspirin, P2 Y12 ADP
0.5 mm or greater, more than two episodes of angina in the past receptor blockers such as clopidogrel, anticoagulants, and GP
24 hours, aspirin use within prior week, or elevated serum car- IIb/IIIa inhibitors) is used to prevent further clotting in the
diac markers. Use of this scoring system was able to risk-stratify coronary artery and allow endogenous fibrinolysis to dissolve
patients across a 10-fold gradient of risk, from 4.7% to 40.9% the thrombus and reduce the degree of coronary stenosis. An-
( p < 0.001) [114]. Most importantly, this risk score identified tithrombotic therapy is continued long term so that if future
patients who derived the greatest benefit from enoxaparin ver- events occur, the degree of thrombosis is reduced. Anti-ischemic
sus UFH [114], from use of a GP IIb/IIIa inhibitor [115], and therapies (e.g., beta-blockers, nitrates, and calcium antago-
from an early invasive management strategy [84]. nists) are used to reduce myocardial oxygen demand. Coro-
The GRACE (Global Registry of Acute Coronary Events) nary revascularization is frequently needed to treat recurrent
risk score also utilized multiple variables to identify those pa- or residual ischemia. After stabilization of the acute event, the
tients who would be at greatest risk of death in the 6 months many factors that led up to the event need to be reversed.
following an ACS. Those variables that conferred the greatest Treatment of atherosclerotic risk factors such as hypercholes-
risk included older age, prior history of congestive heart failure terolemia, hypertension, and cessation of smoking, which con-
or MI, elevated heart rate and relative hypotension at presen- tributes to stabilization of the cholesterol-laden plaque and
tation, the presence of ST-segment depressions, elevated serum healing of the endothelium, is critical.
creatinine at presentation, elevated cardiac biomarkers, and
lack of in-hospital PCI [116]. When applied to patients with
NSTEMI, the GRACE risk score is also able to identify those Aspirin
patients who will benefit most from an early invasive strategy.
In the Timing of Intervention in Patients with Acute Coronary Several major studies have demonstrated clear beneficial effects
Syndromes (TIMACS) trial, NSTEMI patients with a GRACE of aspirin, with a more than 50% reduction in the risk of death
risk score of greater than 140 had a reduction of 35% in the or MI in patients who present with UA/NSTEMI [89,118120].
primary end point (composite of death, MI, or stroke) with Thus, aspirin has had a dramatic effect in reducing adverse
early coronary angiography when compared to delayed inter- clinical events early in the course of treatment of UA/NSTEMI,
vention of greater than 36 hours (13.9% vs. 21%; p = 0.006). and is primary therapy for these patients. An antiplatelet meta-
In patients with a GRACE risk score of less than 140, there analysis found that any dose greater than 75 mg was associ-
was no difference between the two groups (7.6% vs. 6.7%; ated with the same overall benefit [121]. However, preliminary
p = 0.48) [117]. Therefore, combined risk assessment scores data from the Clopidogrel and Aspirin Optimal Dose Usage
can not only identify those patients at the highest risk for an to Reduce Recurrent Events - Seventh Organization to Assess
adverse cardiovascular event, but can also assist the clinician in Strategies in Ischemic Syndromes (CURRENT-OASIS 7) trial,
management decisions regarding angiography and medication presented at the European Society of Cardiology Annual Con-
choices. ference in 2009, showed that patients undergoing PCI who
were treated with double-dose clopidogrel and high-dose as-
pirin (300 to 325 mg) had the lowest rate of cardiovascular
death, recurrent MI, or stroke at 1 year.
MEDICAL THERAPY Bleeding is the main side effect of aspirin, and the rate of
gastrointestinal (GI) bleeding appears to be higher with higher
Treatment Goals doses [121]. Data from the Clopidogrel in Unstable Angina to
Prevent Recurrent Events (CURE) trial have shown that doses
The treatment objectives for patients with UA/NSTEMI are of 75 to 100 mg have a 50% lower rate of major bleeding (2.0%
focused on stabilizing and passivating the acute coronary at 1 year) compared with doses of 200 to 325 mg (4.0% at
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Chapter 38: Unstable Angina/NonST-Segment Elevation Myocardial Infarction 389

1 year); thus, a dose of 75 to 81 mg per day could be the opti- Metabolism of clopidogrel may also be affected by cer-
mal dose for long-term therapy. For acute treatment peri-PCI, tain drugs. Some studies had suggested an interaction between
a dose of 325 mg is generally used. Absolute contraindications clopidogrel and proton pump inhibitors (PPIs), such as omepra-
to aspirin include documented aspirin allergy (e.g., asthma or zole. Initial data, gathered retrospectively from large registries,
anaphylaxis), active bleeding, or a known platelet disorder. In suggested that patients treated with both clopidogrel and a PPI
patients with more minor intolerance to long-term aspirin ther- had worse outcomes than did patients treated with clopido-
apy (e.g., dyspepsia), short-term use of aspirin is recommended grel alone [130]. On discovering this result, researchers began
on the basis of the large early benefit. However, clopidogrel is to investigate possible mechanisms to explain this interaction.
a recommended alternative to aspirin for patients who cannot Indeed, they found that some PPIs have been shown to be
tolerate aspirin [67]. inhibitors of the enzyme, CYP2C19, and they subsequently
hypothesized that simultaneous administration of PPIs and
clopidogrel may lead to competitive metabolism by CYP2C19,
P2 Y12 ADP Receptor Blockers thereby leading to decreased clopidogrel activity. This hypoth-
esis was initially supported by a recent study, which demon-
Clopidogrel is a thienopyridine derivative that inhibits platelet strated that dual administration of clopidogrel and a PPI re-
activation and aggregation by inhibiting the binding of ADP sulted in reduced platelet inhibition when compared to just
to the P2 Y12 receptor on the surface of the platelet. In the clopidogrel alone [131]. However, analysis of data from a clin-
CURE trial, 12,562 patients with UA/NSTEMI were random- ical cohort of the TRITON-TIMI 38 trial demonstrated no
ized to receive aspirin alone (75 to 325 mg per day) or aspirin association between PPI use and clinical outcomes in patients
plus clopidogrel (300-mg loading dose and then 75 mg per on clopidogrel [132]. The safety of the combination of clopi-
day) [122]. The primary end point of cardiovascular death, dogrel and omeprazole was further demonstrated in the Clopi-
MI, or stroke was reduced by 20% (11.4% control vs. 9.3% dogrel and the Optimization of Gastrointestinal Events Trial
clopidogrel; p < 0.0001) [122]. The reduction was seen in all (COGENT), which was recently presented at the 21st An-
subgroups, including patients with ST-segment depression, nual Transcatheter Cardiovascular Therapeutics (TCT) Scien-
those without ST-segment changes, and those with positive or tific Symposium in 2009. This study randomized patients to
negative markers. Interestingly, patients with positive cardiac clopidogrel alone or a combination pill of clopidogrel plus
markers and those with negative markers had similar 20% re- omeprazole following PCI and they found no difference in
ductions in the primary end point. The combination of clopido- cardiovascular outcomes over 4 months, although they did
grel plus aspirin was associated with a relative 35% increase note a significant reduction in GI events in patients taking the
in major bleeding (using the CURE trial definition), but the PPI. Given the dependence of clopidogrel metabolism on the
absolute increase was only 1% (from 2.7% to 3.7%). Further- CYP450 system, certainly extravigilance should be taken when
more, using the standard TIMI definition of bleeding, there was prescribing other drugs with clopidogrel.
no significant increase in major bleeding risk and no increase Although clopidogrel is currently the most utilized P2 Y12
in intracranial hemorrhage. In patients who went on to PCI, ADP receptor blocker, there are two newer generation drugs
a significant 30% reduction was observed through follow-up of the same class that have gained attention in recent years.
[123]. The KaplanMeier event rates began to show a reduc- Prasugrel is a third-generation P2 Y12 ADP receptor blocker.
tion in events starting just 2 hours after randomization. In addi- Although also an irreversible inhibitor, prasugrel has a quicker
tion, when analyzing the benefit in the first 30 days versus after onset of action when compared to clopidogrel (30 to 90 min-
30 days, there was a similar 20% relative risk reduction during utes for prasugrel vs. 4 to 6 hours for clopidogrel) and has lower
both time periods. Thus, it appears that clopidogrel afforded rates of variability in platelet inhibitory effects than clopido-
both an early and an ongoing benefit out to 1 year. grel, thereby resulting in greater platelet inhibition. The ef-
When to start clopidogrel in patients with UA/NSTEMI re- fectiveness of prasugrel in patients with ACS was evaluated
mains a matter of debate. Even with a loading dose, it takes in the TRITON-TIMI 38 trial, in which more than 13,000
several hours before significant antiplatelet effects emerge. For patients, including 10,000 patients with moderate- to high-
this reason, the notion of pretreatment with clopidogrel at least risk UA/NSTEMI and 3,000 patients with STEMI, who were
several hours prior to the PCI has emerged as a possible means scheduled to undergo PCI for treatment of their ACS, were ran-
to help ensure that sufficient platelet inhibition is in effect at domized to receive aspirin and either prasugrel or clopidogrel.
the start of the PCI. Because clopidogrel, like aspirin, is an irre- Patients receiving prasugrel had a 19% reduction in the rate
versible platelet inhibitor, its antiplatelet effect will last for sev- of cardiovascular death, MI, and stroke (9.9% vs. 12.1%; p <
eral days after discontinuation. If a patient is found to require 0.001) as well as a 52% reduction in stent thrombosis (1.1%
surgical revascularization, the procedure should then be put vs. 2.4%; p < 0.001) [133,134] (Fig. 38.5). These positive ef-
off for several days. The guidelines remained silent on the tim- fects come at the price of significantly increased rate of major
ing of clopidogrel. However, across the spectrum of ACS, data bleeding with prasugrel after PCI (2.4% vs. 1.8%; p < 0.001)
have emerged that pretreatment with clopidogrel before a pa- [133].
tient undergoes PCI significantly reduces the risk of death and Ticagrelor is another P2 Y12 ADP inhibitor that has recently
ischemic complications post-PCI [123125]. Thus, the most re- been evaluated. Like prasugrel, ticagrelor has a rapid onset of
cent PCI guidelines now recommend clopidogrel pretreatment action of 1 to 2 hours and greater platelet inhibition than clopi-
before PCI, but they also continue to acknowledge that treat- dogrel; however, in contrast to both prasugrel and clopidogrel,
ment before coronary anatomy is defined remains controversial ticagrelors actions are reversible. The Study of Platelet Inhibi-
[126]. tion and Patient Outcomes (PLATO) study directly compared
Several pharmacogenetic and drugdrug interactions for clopidogrel and ticagrelor in 18,000 patients presenting with
clopidogrel are notable and can affect patient outcomes. Clopi- ACS, about 15,000 of whom were patients with UA/NSTEMIs.
dogrel is a prodrug that requires hepatic biotransformation Ticagrelor significantly reduced the rate of death, MI, or stroke
by CYP450 enzymes into an active metabolite. Approximately when compared to clopidogrel (9.8% vs. 11.7%; p < 0.001)
25% to 30% of the population has a reduced-function genetic (Fig. 38.6) and significantly reduced all-cause mortality by 22%
variant of CYP2C19, a member of the CYP450 enzyme family. [135]. Although there was no significant difference in the rate of
When treated with clopidogrel, these individuals have lower total major bleeding between the two drugs (11.6% vs. 11.2%;
circulating levels of the clopidogrel active metabolite, thereby p = 0.43), a higher occurrence of non-coronary artery bypass
leading to less platelet inhibition, and a higher rate of ischemic grafting surgery (CABG) major bleeding was observed with
events including stent thrombosis [127129]. ticagrelor.
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390 Section III: Cardiovascular Problems and Coronary Care

15

Primary Efficacy End Point Clopidogrel 12.1 138 Events


Hazard ratio, 0.81;
95% CI, 0.730.90;
10 9.9 p < 0.001
End Point (%)

Prasugrel

Key Safety End Point Prasugrel 35 Events


2.4
1.8 Hazard ratio, 1.32;
Clopidogrel 95% CI, 1.031.68;
p = 0.03
0
0 30 60 90 120 150 180 210 240 270 300 330 360 390 420 450
Days after Randomization
No. at Risk
Clopidogrel 6795 6169 6036 5835 5043 4369 3017
Prasugrel 6813 6305 6177 5951 5119 4445 3085

FIGURE 38.5. KaplanMeier curves demonstrating the superiority of prasugrel over clopidogrel in de-
creasing the incidence of the primary efficacy end point (composite of death from cardiovascular causes,
nonfatal myocardial infarction, or nonfatal stroke) over 16 months. Also shown is the KaplanMeir
curve comparing the incidence of the primary safety end point (TIMI major bleeding) between the two
drugshere, prasugrel was associated with an increased risk of TIMI-major bleeding. [From Wiviott SD,
Braunwald E, McCabe CH, et al; for the TRITON-TIMI 38 Investigators: Prasugrel versus clopidogrel in
patients with acute coronary syndromes. New Engl J Med 357:20012015, 2007, with permission.]

Heparin pirin in UA, as recommended in the 2007 ACC/AHA Updated


Unstable Angina Guideline [67].
Heparin appears to be beneficial in UA/NSTEMI [89,136]. A Using the available data, the current optimal regimen ap-
meta-analysis showed a 33% reduction in death or MI at 2 pears to be a weight-adjusted dosing (60 U per kg bolus with a
to 12 weeks follow-up, when comparing heparin plus aspirin maximum of 4,000 U and 12 U per kg per hour infusion with
versus aspirin alone, 7.9% versus 10.4% (relative risk [RR] = a maximum of 1,000 U per hour), frequent monitoring of the
0.67; 95% CI 0.44 to 1.02; p = 0.06) [136] (Fig. 38.7). activated partial thromboplastin time (aPTT) (every 6 hours
Although this reduction did not achieve statistical significance, until in the target range and every 12 to 24 hours thereafter),
these are the data cited to support the use of heparin plus as- and titration using a standardized normogram, with a target

100
12 Clopidogrel
90
10
80
of Primary End Point (%)

8 Ticagrelor
Cumulative Incidence

70
6
60
4
50
2
40
0
30 0 2 4 6 8 10 12
20 FIGURE 38.6. KaplanMeier curves demonstrat-
p < 0.001 ing the superiority of ticagrelor over clopidogrel in
10 decreasing the incidence of the primary efficacy end
point (composite of death from vascular causes,
0 myocardial infarction, or stroke) over 12 months.
0 2 4 6 8 10 12 The primary end point occurred significantly less
Months often with ticagrelor (9.8% vs. 11.7%; p < 0.001).
[From Wallentin L, Becker RC, Budaj A, et al; for
No. at Risk the PLATO Investigators: Ticagrelor versus clopi-
dogrel in patients with acute coronary syndromes.
Ticagrelor 9,333 8,628 8,460 8,219 6,743 5,161 4,147
N Engl J Med 361:10451057, 2009, with permis-
Clopidogrel 9,291 8,521 8,362 8,124 6,650 5,096 4,047 sion.]
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Chapter 38: Unstable Angina/NonST-Segment Elevation Myocardial Infarction 391

Meta-analysis inhibitors. LMWHs are obtained by depolymerization of stan-


Heparin + ASA versus ASA alone dard UFH and selection of those with lower molecular weight
[137,138]. As compared with UFH with its nearly equal anti-IIa
B Theroux (thrombin) and anti-Xa activity, LMWHs have increased ratios
of anti-Xa to anti-IIa activity of either 2:1 (e.g., dalteparin) or
B RISC 3.8:1 (e.g., enoxaparin).
LMWH has several potential advantages over standard
B Cohen UFH. First, it inhibits thrombin as well as factor Xa, thereby
inhibiting thrombin activity and its generation [138]. LMWH
B ATACS
also induces a greater release of tissue factor pathway inhibitor
B Holdright
than UFH and is not neutralized by platelet factor IV [137].
LMWH has been found to have a lower rate of thrombocytope-
B Gurfinkel nia than UFH [139]. Finally, the high bioavailability allows for
Summary Relative Risk subcutaneous administration.
0.67 (0.440.1.02) B Several trials have compared UFH with LMWH in patients
with UA/NSTEMI, and in general, LMWH has been found to
0.1 Heparin + ASA 1 ASA Alone 10 be superior [69,140]. In a meta-analysis of all trials of enoxa-
55/698 = 7.9% 68/655 = 10.4% parin versus UFH in patients with UA/NSTEMI, treatment
RR: Death/MI
with enoxaparin significantly reduced the incidence of recur-
FIGURE 38.7. Meta-analysis of six randomized trials comparing un- rent MI when compared to UFH (8% vs. 9.1%; p = 0.005),
fractionated heparin plus aspirin versus aspirin alone, showing benefit although there was no difference in mortality rates (3% vs.
of the combination therapy. [Adapted from Oler A, Whooley MA, Oler 3%; p = 0.89). Furthermore, treatment with enoxaparin in
J, et al: Adding heparin to aspirin reduces the incidence of myocardial patients with NSTEMIs was not associated with an excess
infarction and death in patients with unstable angina. A meta-analysis. of major bleeding (6.3% vs. 5.4%; p = 0.419) [141] (Fig.
JAMA 276:811815, 1996, with permission.]
38.8). As might be expected, the benefit of enoxaparin ap-
pears greater in patients managed conservatively (who are
range of aPTT between 1.5 and 2.0 times control or approxi- typically on heparin for at least 48 hours) rather than in
mately 50 to 70 seconds [67]. those managed invasively (who go to the catheterization lab-
oratory within 48 hours and have their heparin discontin-
ued thereafter) [142]. Given these results, the 2007 update of
Low-Molecular-Weight Heparin the ACC/AHA Unstable UA/NSTEMI Guideline offers a class
IIa recommendation that enoxaparin be used over UFH, par-
A major advance in the use of heparin has been the develop- ticularly for those patients who are managed conservatively
ment of LMWHs, which are combined thrombin and factor Xa [67].

FIGURE 38.8. Meta-analysis of 12 trials, 6 of which evaluated patients with UA/NSTEMI, which com-
pared UFH with enoxaparin. Data from more than 49,000 patients demonstrated that enoxaparin was
associated with a lower incidence of death of nonfatal MI. CI, confidence interval; ENOX, enoxaparin;
OR, odds ratio; UFH, unfractionated heparin. [From Murphy SA, Gibson CM, Morrow DA, et al: Effi-
cacy and safety of the low-molecular weight heparin enoxaparin compared with unfractionated heparin
across the acute coronary syndrome spectrum: a meta-analysis. Eur Heart J 28:20772086, 2007, with
permission.]
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392 Section III: Cardiovascular Problems and Coronary Care

Several other oral anticoagulants are currently under inves-


Fondaparinux tigation for the treatment of ACS. Rivaroxaban is an oral direct
factor Xa inhibitor, which was initially shown to be effective
Fondaparinux is a synthetic pentasaccharide and a specific Xa in preventing venous thromboembolism after orthopedic surg-
inhibitor. When comparing fondaparinux and enoxaparin, re- eries. The use of rivaroxaban in patients with ACS was stud-
searchers found that the rates of death, MI, or refractory is- ied in the Anti-Xa Therapy to Lower Cardiovascular Events in
chemia throughout the first 9 days were virtually identical with Addition to Aspirin with or without Thienopyridine therapy in
either drug in patients with UA/NSTEMI [143]. The rate of Subjects with Acute Coronary Syndrome (ATLAS-ACS) trial,
major bleeding was nearly 50% lower in the fondaparinux a phase II study, which found that the composite end point of
arm. By 30 days, mortality was significantly lower in the fon- death, MI, or stroke at 6 months was reduced with rivaroxaban
daparinux arm. Notably, in the subset of patients undergoing when compared to placebo (3.9% vs. 5.5%; p = 0.027) [154].
PCI, fondaparinux was associated with more than a threefold Apixaban is another oral direct factor Xa inhibitor, which has
increased risk of catheter-related thrombi. Supplemental UFH recently passed through phase II investigation in the Apixa-
during PCI appeared to minimize this risk, and consequently, ban for Prevention of Acute Ischemic and Safety Events (AP-
the ACC/AHA recommends that UFH and fondaparinux be PRAISE) trial and, similar to rivaroxaban, also demonstrated
used together during PCI. Thus, fondaparinux appears to be a a trend toward a reduction in cardiovascular events [155]. A
new alternative in patients with UA/NSTEMI and is associated third oral direct thrombin inhibitor, dabigatran has gained no-
with a lower risk of bleeding; however, this medication needs tice recently as an alternative to warfarin in stroke prevention
to be used cautiously in patients undergoing PCI. for patients with atrial fibrillation. However, this medication
has also been evaluated for the prevention of recurrent ischemic
Bivalirudin events in patients with acute MI. Initial results from the phase
II RE-DEEM (Randomized Dabigatran Etexilate Dose Find-
Bivalirudin is another antithrombotic drug used in the treat- ing Study in Patients with Acute Coronary Syndromes Post
ment of UA/NSTEMI, which acts by directly inhibiting throm- Index Event with Additional Risk Factors for Cardiovascular
bin and thus inhibiting clot formation. Bivalirudin was eval- Complications Also Receiving Aspirin and Clopidogrel: Multi-
uated in the Acute Catheterization and Urgent Intervention centre, Prospective, Placebo Controlled, Cohort Dose Escala-
Triage Strategy (ACUITY) trial, which randomized 13,820 tion) study, which was presented at the American Heart Associ-
patients with UA/NSTEMI, who were to be managed with ation Scientific Sessions in 2009, reported that dabigatran was
an immediate invasive strategy, to one of three treatments: associated with acceptable bleeding rates and would continue
UFH or enoxaparin plus a GP IIb/IIIa inhibitor, bivalirudin onto phase III studies to evaluate efficacy for use in patients
plus a GP IIb/IIIa inhibitor, or bivalirudin alone. The study with ACS. The clinical efficacy and utilization of these three
found no differences in the primary end point of death, oral antithrombin drugs will be borne out in the ongoing phase
MI, unplanned revascularization for ischemia, and major III trials over the next few years.
bleeding at 30 days between bivalirudin plus GP IIb/IIIa
inhibitor and UFH/enoxaparin plus a GP IIb/IIIa inhibitor
[144]. Furthermore, the similar rate of mortality among the
Thrombolytic Therapy for Unstable
groups was borne out at 1 year of follow-up [145]. For the Angina/NonST-Segment Elevation
bivalirudin-alone group, when compared with the group re- Myocardial Infarction
ceiving UFH/enoxaparin plus a GP IIb/IIIa inhibitor, there were
no differences in the efficacy end point, but a lower rate of Because thrombolytic therapy is beneficial in the treatment of
bleeding was observed (3.0% vs. 5.7%; p < 0.001). Thus, use patients with acute MI presenting with ST-segment elevation,
of bivalirudin in patients receiving GP IIb/IIIa inhibitors did it was hoped that it might play a role in other ACS. In TIMI
not improve efficacy or safety, but the strategy of bivalirudin IIIB, 1,473 patients with UA and nonQ-wave MI were treated
alone was associated with less bleeding than the combination with aspirin and heparin and were randomized to receive
of a GP IIb/IIIa inhibitor with either UFH or enoxaparin [144]. either tissue-type plasminogen activator (t-PA) or its placebo.
No difference was found in the primary end point compar-
ing t-PA with placebo: the incidence of death, postrandomiza-
Oral Anticoagulation tion infarction, or recurrent, objectively documented ischemia
through 6 weeks (54.2% for t-PA and 55.5% for placebo; p =
Oral anticoagulation with warfarin following ACS has been not significant [NS]) [48].
examined in several trials, as prolonged treatment might ex- The TIMI IIIB results are corroborated by the Fibrinolytic
tend the benefit of early anticoagulation with an antithrombin Therapy Trialists Collaborative Group overview, in which pa-
agent. Several trials have found some benefit with initial hep- tients with suspected MI and ST-segment depression on the
arin followed by warfarin [146152]. Most recently, the War- ECG had a higher mortality when treated with a fibrinolytic
farin Reinfarction Study 2 trial randomized 3,630 patients with [156,157]. Accordingly, fibrinolytic therapy is not indicated in
acute MI to three arms: aspirin 160 mg daily; warfarin alone UA/NSTEMI.
(target INR 2.8 to 4.2; mean 2.8); and warfarin (target INR
2.0 to 2.5; mean 2.2) plus 80 mg aspirin [153]. The primary
end point of death, MI, or thromboembolic stroke was lowest Glycoprotein IIb/IIIa Inhibitors
in the combination arm: 20% for aspirin, 16.7% for warfarin,
and 15% for warfarin plus aspirin ( p = 0.0005 for the com- GP IIb/IIIa inhibitors prevent the final common pathway of
bination and p = 0.028 for warfarin alone vs. aspirin) [153]. platelet aggregation, that is, fibrinogen-mediated cross-linkage
The rate of major bleeding was low overall, but was increased of platelets via the GP IIb/IIIa receptor (see Fig. 38.2). Currently
from 0.15% per year for aspirin, to 0.58% for warfarin alone, available GP IIb/IIIa inhibitors include abciximab, eptifibatide,
and 0.52% for warfarin plus aspirin. Thus, the combination and tirofiban. Abciximab is a monoclonal antibody Fab frag-
of warfarin plus aspirin appears to be an effective long-term ment directed at the GP IIb/IIIa receptor, whereas eptifibatide,
treatment for secondary prevention of further cardiovascular a synthetic heptapeptide, and tirofiban, a nonpeptide molecule,
events. However, the difficulty of maintaining warfarin within are antagonists of the GP IIb/IIIa receptor whose structure
a narrow therapeutic window makes the routine use of this mimics the arginineglycineaspartic acid amino acid sequence
medication for this indication inconvenient. by which fibrinogen binds to the GP IIb/IIIa receptor.
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Chapter 38: Unstable Angina/NonST-Segment Elevation Myocardial Infarction 393

Intravenous GP IIb/IIIa Inhibitors in ACS:


Death or MI at 30 Days
Study Placebo IV GP IIb/IIIa Odds Ratio 95% CI
PRISM 7.1% 5.8%a 0.80 0.601.06
PRISM-PLUS 12.0% (l) 8.7% 0.70 0.500.98
(h) 13.6%a 1.17 0.801.70
PARAGON-A 11.7% (l) 10.3% 0.87 0.581.29
(h) 12.3% 1.06 0.721.55
PURSUIT 15.7% (l) 13.4% 0.83 0.700.99
(h) 14.2% 0.89 0.791.00
PARAGON-B 11.4% 10.6% 0.92 0.771.09
GUSTO-IV 8.0% (24 h) 8.2% 1.02 0.831.24 FIGURE 38.9. Meta-analysis of the
(48 h) 9.1% 1.15 0.941.39 benefit of IV GP IIb/IIIa inhibitors
in acute coronary syndrome (ACS):
Overall 11.8% 10.8%b 0.91 0.850.99 death or myocardial infarction (MI) at
30 days. [From Boersma E, Harring-
0.0 1.0 2.0 ton RA, Molterno DJ, et al: Platelet
GP IIb/IIIa Better Placebo Better glycoprotein IIb/IIIa inhibitors in
Odds Ratio (95% CI) acute coronary syndromes: a meta-
analysis of all major randomized clini-
a Without
cal trials. Lancet 359:189198, 2002,
heparin; b with/without heparin; (l), low dose; (h), hi gh dose. with permission.]

The efficacy of the GP IIb/IIIa inhibitors in the treatment Later studies did not yield the same results. The GUSTO-IV
of NSTEMIs has been demonstrated in several studies. In the ACS trial failed to show a benefit of abciximab when given
PRISM-PLUS trial involving 1,915 patients with UA/NSTEMI, upstream of PCI [160]. In addition, the ACUITY-Timing study
tirofiban plus heparin and aspirin led to a significantly lower found that early administration of GP IIb/IIIa inhibitors did
rate of death, MI, or refractory ischemia at 7 days than did not reduce recurrent ischemia when compared to selective ad-
placebo (i.e., heparin plus aspirin) (12.9% vs. 17.9%, a 32% ministration of the medication in the catheterization laboratory
risk reduction; p = 0.004). These results were borne out at 30 during PCI (7.1% vs. 7.9%; p = 0.44), although bleeding was
days as well [49]. (Death or MI was reduced by 30%, from significantly increased with upstream administration (6.1% vs.
11.9% to 8.7%; p = 0.03.) In the PURSUIT (Platelet Glyco- 4.9%; p < 0.001) [161]. More recently, the EARLY ACS (Early
protein IIb/IIIa in Unstable Angina: Receptor Suppression us- Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation
ing Integrillin Therapy) trial, which involved 10,948 patients, Acute Coronary Syndrome) trial evaluated the use of routine
eptifibatide reduced the rate of death or MI at 30 days by a use of upstream GP IIb/IIIa inhibitor eptifibatide versus delayed
relative 10% (from 15.7% to 14.2%; p = 0.042). A greater provisional use of the medication at the time of PCI [162]. In
benefit was observed in patients who were treated with an early this trial, more than 9,000 patients with UA/NSTEMI, who
invasive strategy with early PCI plus eptifibatide (31% reduc- were planned for an early invasive strategy with early PCI, were
tion in death or MI at 30 days; 16.7% vs. 11.6%; p = 0.01), assigned to either receive upstream eptifibatide for the 12+
whereas the relative benefit was less (7% reduction; p = 0.23) hours prior to catheterization or to the provisional use of epti-
in those treated conservatively with delayed PCI or CABG as fibatide after angiography. There was no significant difference
needed [71]. The benefit of GP IIb/IIIa inhibition appears to in the composite rate of death, MI, urgent revascularization, or
be restricted to troponin-positive patients (i.e., those patients thrombotic complication during PCI between the two groups.
with true NSTEMIs) as demonstrated in the ISAR-REACT 2 Although GP IIb/IIIa inhibitors may be efficacious in pre-
trial, which studied 2,022 patients and found that abciximab venting adverse cardiovascular events, there are serious side
reduced the risk of adverse cardiovascular events by 25% only effects associated with this class of drug. Several studies have
in patients with NSTEMIs being treated with PCI [96]. There demonstrated that the rate of major hemorrhage is slightly
was no difference in cardiovascular events in patients with UA higher for patients treated with GP IIb/IIIa inhibitors. In
and a normal troponin level. PRISM-PLUS, major bleeding occurred in 4% of patients
Although GP IIb/IIIa drugs certainly appear to be useful in treated with tirofiban plus heparin plus aspirin versus 3.0%
the management of patients with NSTEMIs, who are undergo- for heparin plus aspirin ( p = NS) [49]. For eptifibatide, the
ing PCI, the question remains as to what the optimal time for rates of severe or moderate bleeding with eptifibatide versus
administration of the drug is. Initial analyses of data suggested placebo were 12.8% and 9.9%, respectively ( p < 0.001) [71].
that perhaps early administration of a GP IIb/IIIa inhibitor was In EARLY ACS, patients who were given upstream eptifibatide
beneficial. A meta-analysis of three trials (PRISM-PLUS, PUR- had higher rates of nonlife-threatening bleeding (5.8% vs.
SUIT, and CAPTURE [c7E3 antiplatelet therapy in unstable 3.4%; p < 0.001) and more blood transfusions (8.6 vs. 6.7;
refractory angina]) involving 12,296 patients yielded a 34% p = 0.001) [162].
relative reduction in death or MI with the early use of the GP Thrombocytopenia is also more common with GP IIb/IIIa
IIb/IIIa antagonists, although the absolute difference in event inhibitors. For tirofiban in PRISM-PLUS, the rate of severe
rates was small (3.8% vs. 2.5%; p = 0.001) [158]. As was ex- thrombocytopenia (<50,000 cells per mm3 ) was 0.5%, ver-
pected, an even greater benefit was seen when the agents were sus 0.3% for heparin ( p = 0.44). The latter event is associated
continued during PCI (8.0% vs. 4.9%; p = 0.001). These find- with increased bleeding and in a smaller proportion of patients,
ings were confirmed, although less robustly, in a more recent recurrent thrombotic events [163,164]. This syndrome bears
meta-analysis involving six trials, which again found that the resemblance to heparin-induced thrombocytopenia and indi-
use of GP IIb/III antagonists resulted in a 9% relative reduction cates a need to monitor platelet count daily during the GP
in death or MI when compared to placebo [159] (Fig. 38.9). IIb/IIIa infusion.
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394 Section III: Cardiovascular Problems and Coronary Care

Despite the risks associated with the GP IIb/IIIa inhibitors, events [187189]. Some meta-analyses have found no benefi-
the current ACC/AHA guidelines support the use of GP IIb/IIIa cial effect in reducing mortality or subsequent infarction with
inhibitors during PCI in patients with UA/NSTEMI [67]. Nev- calcium channel blockers [171,190,191]. Furthermore, in pa-
ertheless, the use of a GP IIb/IIIa inhibitor upstream of planned tients with acute MI with significant LV dysfunction or heart
PCI for UA/NSTEMI is now in question and further studies are failure, a harmful effect has been observed with the administra-
needed to see if particular subgroups benefit from upstream tion of certain calcium channel blockers [192]. Nifedipine has
administration of this medication. When GP IIb/IIIa inhibitors been shown to be harmful in patients with acute MI when not
are used either during PCI or with conservative management coadministered with a beta-blocker in the trial of Early Nifedip-
of UA/NSTEMI, the benefit does appear to be greatest in pa- ine Treatment in Acute Myocardial Infarction [193,194]. Thus,
tients at higher risk (i.e., those who have a positive troponin the current guidelines recommend that calcium channel block-
at baseline [96,98100,165], those with diabetes [166], those ers be used only in patients with preserved LV function and
with recurrent angina, or those with prior aspirin use [167]). without heart failure, and then only if needed for recurrent
ischemia despite beta-blockade or for patients in whom beta-
blockade is contraindicated [67].
Anti-Ischemic Therapy
Ranolazine
Nitrates Although the exact mechanism of its antianginal effects is un-
Nitrates are very useful in the acute management of ischemia known, ranolazine has been shown to partially inhibit fatty
and should be given sublingually if the patient is experiencing acid oxidation and may improve the efficiency of oxygen uti-
ischemic pain. Nitrates are provided for symptom relief and do lization in the myocyte. In the Combination Assessment of Ra-
not impart a mortality benefit. Both the Gruppo Italiano per nolazine in Stable Angina (CARISA) trial, researchers found
lo Studio della Sopravvivenza nellInfarto miocardico 3 and that patients with stable angina, who were treated with ra-
International Study of Infarct Survival (ISIS) 4 trials failed to nolazine in addition to beta-blockers or calcium channel block-
demonstrate a survival benefit with nitrates in patients with ers, had fewer episodes of angina (one episode less per week
suspected ACS, either in the overall population of subjects or than placebo; p < 0.02) and showed increased exercise capac-
in the subgroup of patients with NSTEMI [168,169]. If pain ity (115.6 seconds vs. 91.7 seconds; p = 0.01) [195]. Similar
persists after three sublingual tablets and initiation of beta- results reflecting the anti-anginal effects of ranolazine in pa-
blockade, intravenous nitroglycerin is recommended [67]. Be- tients with chronic stable angina were demonstrated in the
cause the goal of nitrate therapy is relief of pain, nitrates can MARISA (Monotherapy Assessment of Ranolazine in Sta-
frequently be tapered off during hospitalization. ble Angina) trial [196]. The Metabolic Efficiency with Ra-
nolazine for Less Ischemia in Non-ST Elevation Acute Coro-
Beta-Blockers nary Syndrome (MERLIN)-TIMI 36 trial expanded the use of
Several placebo-controlled trials in UA/NSTEMI have shown ranolazine to the NSTEMI population by evaluating 6,560 pa-
benefit of beta-blockers in reducing subsequent MI, recurrent tients with NSTEMIs, 3,279 of whom were randomized to
ischemia, or both [170174]. Early intravenous beta-blockade receive ranolazine and 3,281 of whom received placebo. Al-
appears to provide early benefits in UA/NSTEMI [175]. In though there was no difference in the primary end point (a
early studies performed in the prethrombolytic era that in- composite of cardiovascular death, MI, or recurrent ischemia)
cluded patients with ST-segment elevation MI and NSTEMI, between the two groups (21.8% vs. 23.5%; p = 0.11), there
beta-blockers were shown to reduce infarct size, reinfarction, was a significant reduction in the rates of recurrent ischemia
and mortality [176179]. This beneficial effect of beta-blockers with ranolazine (13.9% vs. 16.1%; p = 0.03) [197]. Follow-up
(intravenous followed by oral) has also been seen in subgroup analyses of the MERLIN-TIMI 36 trial confirmed the results of
analyses of patients with NSTEMI [179181]. the CARISA and MARISA trials and demonstrated that anginal
Beta-blockers are recommended for patients with UA/ symptoms were improved with ranolazine (HR 0.77; 95% CI
NSTEMI who do not have contraindications to their use 0.59 to 1.00; p = 0.048) [198]. Hence, ranolazine remains an
(bradycardia, advanced atrioventricular block, persistent hy- attractive addition to beta-blockers and nitrates for treatment
potension, pulmonary edema, and history of bronchospasm). of chronic, severe angina.
If ischemia and chest pain are ongoing, early intravenous beta-
blockade should be used, followed by oral beta-blockade. It Angiotensin-Converting Enzyme Inhibitors
should be noted that a reduced ejection fraction is no longer a Angiotensin-converting enzyme (ACE) inhibitors have been
contradiction to beta-blockade, and indeed, such patients may shown to be beneficial in patients after MI, who have either LV
derive added benefit given the salutary effects seen with long- systolic dysfunction (ejection fraction <40%) [199] or heart
term beta-blockade in patients with heart failure [182184]. failure [200]. The Gruppo Italiano per lo Studio della So-
However, beta-blockers should not be initiated in patients with pravvienza nellInfarto miocardico-3, ISIS-4, and Chinese trials
evidence of decompensated heart failure until they have become showed a 0.5% absolute mortality benefit of early (initiated
hemodynamically stable [185]. within 24 hours) ACE inhibition in patients with acute MI
[168,169]. However, in the ISIS-4 study, no benefit was ob-
Calcium Channel Blockers served in patients without ST-segment elevation. Thus, early
Calcium channel blockers may be used in patients who have routine ACE inhibition does not appear to confer survival ben-
persistent or recurrent symptoms, but they are currently recom- efit for patients with UA or NSTEMI.
mended only after nitrates and beta-blockade have been initi- On the other hand, long-term use of ACE inhibition is appli-
ated [67]. In patients with contraindications to beta-blockade, cable to several groups of patients with cardiovascular disease,
improved heart rate control can be accomplished with some including those with LV systolic dysfunction [199]. Data based
calcium channel blockers (e.g., diltiazem or verapamil). The on evidence from the Heart Outcomes Prevention Evaluation
Diltiazem Reinfarction Study, which involved 576 patients with trial suggests that ACE inhibition prevents recurrent cardio-
nonQ-wave MI, showed that diltiazem reduced the rate of re- vascular events in patients with prior MI, peripheral arterial
current MI from 9.3% with placebo to 5.2% with diltiazem disease, or diabetes, even if ventricular function is preserved
[186]. Furthermore, some studies have suggested that the use [201]. Similar results were also seen in the European Trial on
of amlodipine in stable patients with high-risk cardiovascu- Reduction of Cardiac Events with Perindopril in Stable Coro-
lar features can decrease the incidence of major cardiovascular nary Artery Disease (EUROPA) trial [202]. However, a third
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Chapter 38: Unstable Angina/NonST-Segment Elevation Myocardial Infarction 395

trial, the Prevention of Events with Angiotensin Converting En- An early benefit on overall clinical outcome has been
zyme [ACE] inhibitor (PEACE) trial, did not show any benefit found in the Myocardial Ischemia Reduction with Aggressive
with routine use of trandolapril in this population of patients, Cholesterol Lowering (MIRACL) trial. In 3,086 patients with
perhaps because the patients in this study were relatively low UA/NSTEMI, atorvastatin 80 mg as compared to placebo was
risk and had been treated with more intensive statin therapy found to reduce the rate of the composite end point of death,
and more frequent coronary revascularization [203]. MI, cardiac resuscitation, and angina, leading to rehospitaliza-
tion by 4 months [210]. Further analysis demonstrated that this
Angiotensin Receptor Blockers difference was mostly due to a reduction in the rate of rehospi-
Angiotensin receptor blockers (ARBs) provide an alternative to talization for angina. In the Pravastatin or Atorvastatin Evalu-
ACE inhibitors, and may block the reninangiotensin system ation and Infection Therapy (PROVE-IT) TIMI 22 trial, inten-
more completely than ACE inhibitors, because angiotensin II sive lipid-lowering therapy with atorvastatin 80 mg resulted in
can be generated via pathways that are independent of ACE a 16% reduction in the primary end point and a 25% reduc-
[204]. The Valsartan in Acute Myocardial Infarction Trial tion in death, MI, or urgent revascularization, when compared
(VALIANT) was one of the first trials to directly compare with only moderate lipid-lowering therapy with pravastatin
ARBs and ACE inhibitors. In this study, about 15,000 pa- 40 mg [211]. The benefits emerged after only 30 days post-ACS
tients with a history of MI that was complicated by heart fail- [212], highlighting the importance of early initiation of inten-
ure were randomized to receive either an ARB (valsartan), an sive statin therapy post-ACS. When comparing the two arms
ACE inhibitor (captopril), or a combination of the two drugs of this study, it was noted that there was a significant difference
[205]. Valsartan was found to be noninferior to captopril at in the LDLs achieved in each group. The average LDL achieved
2 years with regard to mortality ( p = 0.004) and with regard was 62 mg per dL in the atorvastatin 80 mg group and 95 mg
to recurrent cardiovascular events ( p < 0.001). The VALIANT per dL in the pravastatin 40 mg group. Based in part on these
trial was subsequently followed by the On-going Telmisartan results, the adult treatment panel III of the National Choles-
Alone and In Combination with Ramipril Global Endpoint terol Education Program issued an update in which they recom-
Trial (ON-TARGET), which randomized patients with known mended a new optional very low LDL goal of less than 70 mg
vascular disease or diabetes to receive either telmisartan, an per dL in patients with high-risk coronary heart disease [213].
ARB, or ramipril, an ACE inhibitor, or both drugs together
[206]. Again, the ARB was shown to be noninferior to the
ACE inhibitor with similar rates of death, MI, stroke, or hos- TREATMENT STRATEGIES AND
pitalization for heart failure at 56 months (16.5% vs. 16.7%;
RR 1.01; 95% CI 0.94 to 1.09). Furthermore, patients who
INTERVENTIONS
received telmisartan had less complaints of cough (1.1% vs.
4.2%; p < 0.001) when compared to those receiving the ACE Early Invasive Versus Ischemia-Guided
inhibitor. Hence, ARBs remain effective alternatives to ACE Strategy of Revascularization
inhibitors and may even be better tolerated.
Two general approaches to the use of coronary angiography
Lipid-Lowering Therapy
and revascularization in UA/NSTEMI exist. The first is an
Long-term treatment with lipid-lowering therapy with statins early invasive strategy, involving routine angiography and
has been shown to be beneficial in patients with a prior his- revascularization with PCI or bypass surgery as appropriate.
tory of either MI or UA [207209]. In individuals with UA in The other is a more conservative approach with initial medical
the Long-term Intervention with Pravastatin in Ischemic Dis- management with angiography and revascularization only for
ease Trial, pravastatin led to a 26% reduction in mortality recurrent ischemia, which could be termed an ischemia-guided
( p = 0.004), as well as significant reductions in subsequent MI, strategy. Eight randomized trials have assessed these two gen-
coronary revascularization, and stroke [209]. eral strategies [48,66,73,74,84,117,214] (Fig. 38.10).

FIGURE 38.10. Meta-analysis of the benefit of a routine invasive versus selective invasive (i.e., con-
servative) strategy for patients with unstable angina or NSTEMI. ACS, acute coronary syndrome. Rate
of death or MI or rehospitalization with ACS through follow-up. [From ODonoghue M, Boden WE,
Braunwald E, et al: Early invasive vs conservative treatment strategies in women and men with unstable
angina and non-ST-segment elevation myocardial infarction: a meta-analysis. JAMA 300(1):7180, 2008,
with permission.]
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396 Section III: Cardiovascular Problems and Coronary Care

The initial trials showed no benefit with an early invasive a reduction in refractory angina. Interestingly by 5 years, there
strategy. Subsequently, the FRISC II trial was conducted after was a significantly lower cardiovascular mortality rate in the
coronary stenting had become available and found a significant early invasive arm [219].
benefit with an invasive strategy for the risk of death or MI The Invasive versus Conservative Treatment in Unstable
at 6 months (9.4% vs. 12.1%; p = 0.031) [215]. At 1 year, Coronary Syndromes (ICTUS) trial also examined an invasive
there was a significant reduction in mortality in the invasive versus conservative approach in 1,200 patients. All patients re-
versus conservative groups (2.2% vs. 3.9%, respectively; p = ceived aspirin, enoxaparin, and abciximab at the time of PCI.
0.016) and in death or MI (10.4% vs. 14.1%, respectively; At 1 year, there was no significant difference in the rate of the
p = 0.005) [215]. Additional analyses showed greater benefit composite primary end point of death, MI, or rehospitaliza-
with the invasive strategy in higher risk groups identified by tion for angina [220]. In fact, during the index hospitalization,
ST-segment depression on the admission ECG or troponin T there was a higher rate of MI in the invasive arm. In contrast,
greater than or equal to 0.01 ng per dL [216,217]. the risk of spontaneous MI tended to be lower (RR 0.80, 95%
Subsequently, the TACTICS-TIMI 18 trial, wherein all pa- CI 0.46 to 1.34), and the risk of rehospitalization for angina
tients were treated with an upstream GP IIb/IIIa inhibitor, was significantly lower in the invasive arm (RR 0.68, 95% CI
found a significant reduction in death, MI, or rehospitalization 0.47 to 0.98).
for an ACS at 6 months with use of the early invasive strategy Most recently, the TIMACS trial tackled the question of
(from 19.4% in the conservative group to 15.9% in the early timing of an invasive management strategy in 3,031 patients
invasive strategyOR, 0:78; p = 0.025) [84]. Similarly, death presenting with UA/NSTEMI. Patients were randomized to un-
or nonfatal MI was significantly reduced at 30 days (7.0% to dergo either early angiography within the first 24 hours of
4.7%, respectively; p = 0.02) and at 6 months ( p = 0.0498). randomization or delayed angiography anytime after 36 hours
These effects were most magnified in patients with ST-segment after randomization. Similar to the ICTUS trial, at 6 months,
changes, in those with positive troponin values compared with there was no significant difference in the rate of the composite
negative values, and in those with intermediate or high TIMI primary end point of death, MI, or stroke [117]. Nevertheless,
risk scores. In patients with a troponin I of greater than or equal subgroup analyses demonstrated that patients considered high
to 0.1 ng per mL, there was a relative 39% risk reduction in the risk did benefit from early invasive therapy with a significant
primary end point with the invasive versus conservative strat- reduction in the primary outcome of 13.9% versus 21% in the
egy ( p < 0.001), whereas patients with a negative troponin had delayed intervention group (HR 0.65; 95% CI 0.48 to 0.89;
similar outcomes with either strategy [91]. Using the TIMI risk p = 0.006). Furthermore, for patients of all risk groups, the
score, there was significant benefit of the early invasive strategy secondary outcome of death, MI, and refractory ischemia was
in intermediate- (score 3 to 4) and high-risk patients (5 to 7), significantly reduced in the early invasive group (9.5%) as op-
whereas low-risk (0 to 2) patients had similar outcomes when posed to the delayed intervention group (12.9%) (HR 0.72;
managed with either strategy [84]. 95% CI 0.58 to 0.89; p = 0.003).
Randomized Intervention Treatment of Angina (RITA) 3 Using the available data, an early invasive strategy is likely
tested an early invasive versus conservative approach in 1,810 superior to a conservative strategy in reducing cardiac events,
patients with UA/NSTEMI, all of whom were managed with in particular spontaneous MI after hospital discharge and re-
enoxaparin [218]. An invasive strategy again proved superior, fractory ischemia. This benefit appears greatest in patients at
although the 34% reduction in the primary end point of death, intermediate or high risk (especially those with positive tro-
MI, or refractory angina at 4 months was driven primarily by ponin). In contrast, lower risk patients have similar outcomes

Non-ST
Noncardiac Stable Unstable ST
Elevation
Chest Pain Angina Angina Elevation MI
MI

Atypical Exertional Rest Pain; Multiple Cardiac Ongoing


Clinical Finding
Pain Pain Risk Factors Pain

ST-T wave
EKG Negative ST Elevation
Changes

Serum Markers Negative Positive

Low
Risk Assessment Low Risk Medium/High Risk STEMI
Probability

Aspirin; Clopidogrel/Prasugrel;
FIGURE 38.11. Algorithm for risk strat-
Diagnostic Rule Thrombolysis ification and treatment of patients with
UFH/LMWH; Anti-ischemic Primary PCI
out MI/ACS therapy; UA/NSTEMI. ACS, acute coronary syn-
Pathway Positive Early conservative Rx drome; DM, diabetes mellitus, ECG, electro-
cardiogram; LMWH, low-molecular-weight
Negative Aspirin; Clopidogrel/Prasugrel; GP heparin; MI, myocardial infarction, Rx,
IIb/IIIa Inhibitor; UFH/LMWH/ treatment, STEMI, ST-segment elevation my-
Bivalirudin; Anti-ischemic Therapy ocardial infarction; UFH, unfractionated
Discharge Early invasive Rx heparin.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 38: Unstable Angina/NonST-Segment Elevation Myocardial Infarction 397

with either strategy, meaning that either a conservative or in- TA B L E 3 8 . 3


vasive strategy can be used in low-risk patients. These results
have been incorporated into the update of the ACC/AHA and ADVANCES IN MANAGING UA/NSTEMI
European Society of Cardiology guidelines for UA/NSTEMI,
which recommend broader use of an early invasive strategy. Identification of high-risk patients is key to management of
UA/NSTEMI [64,90,97101]
Aspirin leads to a more than 50% reduction in the risk of
death or myocardial infarction [88,112114]
Percutaneous Coronary Intervention Versus The addition of clopidogrel to aspirin further reduces risk
by 20% [116], especially when given prior to percutaneous
Coronary Artery Bypass Graft coronary intervention [117119]. Prasugrel and ticagrelor
When revascularization is indicated, the choice between PCI are alternative P2 Y12 ADP receptor blockers that have been
versus surgery is faced. In the acute setting, PCI is undertaken shown to be superior to clopidogrel in the treatment of
much more frequently than CABG surgery. The presence of sig- NSTEMI
Anticoagulation with one of four agents has been shown to
nificant left main coronary artery disease leads to early surgery,
with the expectation of improved survival relative to medical be beneficial: heparin [121], low-molecular-weight heparin
therapy alone [221,222]. Six comparative trials have compared (dalteparin and enoxaparin) [128,129], fondaparinux
PCI with CABG in the nonacute setting; both revascularization [133], or bivalirudin [136]
Glycoprotein IIb/IIIa inhibitors can be considered in
strategies resulted in similar rates of death, but a greater need
for additional procedures was seen in those initially treated troponin-positive patients [9699]; however, the benefit of
with PCI [223228]. The SYNTAX (Synergy between Per- upstream administration in patients undergoing urgent
cutaneous Coronary Intervention with TAXUS and Cardiac percutaneous coronary intervention is questionable [162]
Early, intensive statin therapy is beneficial [186,187]
Surgery) trial recently compared PCI with CABG in 1,800 pa-
An early invasive strategy is beneficial in intermediate- and
tients with three-vessel or left main coronary artery disease and
confirmed these prior findingsthe rates of death were similar high-risk patients [76,117,198]
between the two groups, though the PCI group experienced rel-
UA-NSTEMI, unstable angina/nonST-segment elevation myocardial
atively more major adverse cardiac or cerebrovascular events infarction.
over the time course of the study (17.8% vs. 12.4% for CABG;
p = 0.002) largely because of an increased rate of repeat revas-
cularization with PCI (13.5% vs. 5.9% for CABG; p < 0.001)
[228]. There was a higher rate of early stroke with CABG
surgery. Differences in mortality with PCI and CABG were CONCLUSIONS
noted in certain subgroups. In the Bypass Angioplasty Revascu-
larization Investigation trial, patients with diabetes who were An overall approach to patient management is shown in Fig-
treated surgically with a left internal thoracic artery graft were ure 38.11. Using the medical history, ECG, and cardiac mark-
noted to have a significantly lower mortality compared with ers, one can identify patients who have a low likelihood of
angioplasty [227]. This finding was further supported by a re- UA/NSTEMI, for whom a diagnostic rule-out MI or ACS
cent meta-analysis of ten randomized trials comparing PCI and is warranted. If this work-up is negative, the patient is dis-
CABG in patients with multivessel coronary disease in which charged home; if positive, the patient is admitted and treated
mortality was shown to be lower with CABG in patients with for UA/NSTEMI. These patients are treated with aspirin, a
diabetes or in those older than 65 years [229]. Using these data P2 Y12 ADP receptor blocker (either clopidogrel or prasugrel,
and those of previous trials of CABG versus medical therapy or perhaps ticagrelor in the future), an anticoagulant (UFH or
[221,222,230,231] and more recent observational data [232], LMWH if at a low risk for bleeding, or bivalirudin if at high
CABG is recommended for patients with disease of the left risk for bleeding), and anti-ischemic therapy with nitrates and
main coronary artery, multivessel disease involving the prox- beta-blockers. Risk stratification is used to identify patients at
imal left anterior descending artery, multivessel disease, and medium to high risk, for whom aggressive treatment with an
impaired LV systolic function or multivessel disease and di- early invasive strategy is warranted. For patients at low risk,
abetes [229,233]. For other patients, either PCI or CABG is standard treatment is likely sufficient, and a more conservative
suitable. PCI has a lower initial morbidity and mortality than approach would be reasonable.
CABG but a higher rate of repeat procedures, whereas CABG is Advances in UA/NSTEMI, based on randomized controlled
associated with more effective relief from angina and the need trials or meta-analyses of such trials, are summarized in Table
for fewer medications. 38.3.

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Heart Foundation RITA 3 randomised trial. Lancet 366(9489):914920, 232. Mark DB, Nelson CL, Califf RM, et al: Continuing evolution of therapy for
2005. coronary artery disease. Initial results from the era of coronary angioplasty.
220. De Winter RJ, Windhausen F, Cornel JH, et al: Early invasive versus selec- Circulation 89:20152025, 1994.
tively invasive management for acute coronary syndromes. N Engl J Med 233. Hillis LD, Rutherford JD: Coronary angioplasty compared with bypass
353(11):10951104, 2005. grafting. N Engl J Med 331:10861087, 1994.

CHAPTER 39 ST-SEGMENT ELEVATION


MYOCARDIAL INFARCTION
JAMES A. de LEMOS AND DAVID A. MORROW

Advances in the prevention, diagnosis, and management of pa- not associated with critical narrowing of the arterial lumen.
tients with acute ST-segment elevation myocardial infarction Molecular factors that regulate synthesis and dissolution of
(STEMI) have led to a reduction in mortality from this condi- the extracellular matrix appear to modulate integrity of the
tion over the past few decades [1]. Rapid delivery of reperfusion protective fibrous cap. In unstable atherosclerotic lesions, in-
therapy remains the cornerstone of management of STEMI. In flammatory cells accumulate at the shoulder region of the
recent years, substantial improvements in adjunctive therapies plaque and release cytokines that degrade extracellular matrix
and processes of care delivery have been made, and these are and weaken the fibrous cap at this critical site [2].
expected to contribute to continued improvement in outcomes Following plaque rupture, platelets adhere to subendothe-
following STEMI. lial collagen, von Willebrand factor, or fibrinogen, and become
activated by various local mediators such as adenosine diphos-
phate (ADP), collagen, and thrombin. Activated platelets un-
PATHOPHYSIOLOGY dergo a conformational change and secrete the contents of
their -granules, promoting vasoconstriction and clot retrac-
The initial pathophysiologic event leading to STEMI is rupture tion. Activated platelets also express glycoprotein (GP) IIb/IIIa
or erosion of a lipid-rich atherosclerotic plaque. The atheroscle- receptors in increased number and with greater binding affin-
rotic plaque vulnerable to rupture tends to have a dense ity; fibrinogen-mediated cross-linking at this critical receptor
lipid-rich core and a thin protective fibrous cap, and is often leads to platelet aggregation. On the phospholipid surface of
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Chapter 39: ST-Segment Elevation Myocardial Infarction 403

TA B L E 3 9 . 1
DIFFERENTIAL DIAGNOSIS OF ACUTE MI

Characterization Helpful diagnostic


Condition of pain Physical findings ECG findings tests

Acute coronary Pressure-type pain at Examination often ST-segment elevation, Measurement of


syndrome rest, often radiating normal; check for ST-segment depression, cardiac enzymes
to neck or left arm signs of cardiogenic T-wave abnormalities,
shock or CHF LBBB
Tako-Tsubo Similar to AMI, but Examination often Anteroapical ST-segment Cardiac enzymes only
cardiomyopathy commonly normal; may have elevation commonly minimally elevated;
precipitated by signs of CHF with T-wave inversion anteroapical
emotional stress akinesis; normal
coronary arteries
Aortic dissection Tearing pain Diminished pulse or Nonspecific changes, Chest x-ray, CT scan,
radiating to back blood pressure in LVH; ST-segment or MRI;
left arm elevation if dissection transesophageal
involves coronary ostia echocardiography;
aortogram
Pulmonary embolism Pleuritic chest pain Tachypnea; Sinus tachycardia with High-resolution chest
with dyspnea and tachycardia; pleural nonspecific ST and CT; ventilation-
cough rub; right T-wave changes; perfusion lung scan;
ventricular heave S1 Q3 T3 pattern classic, pulmonary
but rarely seen angiogram
Pericarditis Positional pain (worse Pericardial friction rub Diffuse, concave Echocardiogram
lying flat) ST-segment elevation
with PR-segment
depression

CT, computed tomography; CHF, congestive heart failure; LBBB, left bundle branch block; MRI, magnetic resonance imaging.

the platelet membrane prothrombin is converted to thrombin, in 25% or more cases. Characterization of the quality of the
catalyzing the conversion of fibrinogen to fibrin [3]. pain may help to distinguish MI from other conditions that
The distinguishing feature of the plateletfibrin clot in cause chest discomfort, such as aortic dissection, pulmonary
STEMI is that it completely occludes the epicardial coronary embolism, pericarditis, and gastrointestinal (GI) disorders such
artery, leading to transmural myocardial injury, manifested by as cholecystitis and peptic ulcer (Table 39.1).
ST-segment elevation on the electrocardiogram (ECG). Despite Patients with acute MI often appear pale and clammy; in
similar initial pathophysiologic features, unstable angina and many cases, they are in obvious distress. Elderly patients, in
non-STEMI (NSTEMI) are rarely associated with complete oc- particular, may be agitated and incoherent. In contrast, pa-
clusion of the culprit coronary artery and do not benefit from tients with cardiogenic shock may be confused and listless. The
fibrinolytic therapy. The distinction between Q-wave and non objective of the initial examination should be to rapidly nar-
Q wave MI can only be made retrospectively, and is not use- row the differential diagnosis and assess the stability of the
ful for early patient management. Accordingly, this terminol- patient. A focused examination can help to differentiate is-
ogy has been superseded by the terms STEMI and NSTEMI. chemia from conditions such as pneumothorax, pericarditis,
Without reperfusion therapy, most patients with STEMI suffer aortic dissection, and cholecystitis (Table 39.1). Concomitant
transmural infarction and evolve Q-waves over the first few conditions, such as valvular heart disease, peripheral vascular
days after MI. Successful reperfusion therapy, however, may disease, and cerebrovascular disease, may complicate patient
limit necrosis to the subendocardial regions and prevent devel- management and can be rapidly detected by physical examina-
opment of Q-waves. tion. A brief survey for signs of congestive heart failure should
be performed. Cool extremities or impaired mental status sug-
gests decreased tissue perfusion, whereas elevated jugular ve-
DIAGNOSIS AND RISK nous pressure and rales suggest elevated cardiac filling pres-
sures. Finally, the hemodynamic and mechanical complications
ASSESSMENT of acute MI can often be detected by careful attention to phys-
ical findings.
History and Physical Examination An increasingly recognized syndrome that may mimic acute
MI is Tako-Tsubo cardiomyopathy, or the apical balloon-
The pain of acute MI is qualitatively similar to angina and is ing syndrome. This syndrome, more common among elderly
classically described as a severe pressure-type pain in the mid- women, is typically precipitated by an acute stress, includ-
sternum, often radiating to the left arm, neck, or jaw. Asso- ing severe emotional distress or acute noncardiac medical
ciated symptoms include dyspnea, diaphoresis, nausea, vom- illness. Chest pain associated with anteroapical ST-segment ele-
iting, and weakness. In the elderly and those with diabetes, vation and T-wave inversions is usually indistinguishable from
pain is often atypical, and may not be present at all [4]. Not an evolving anterior infarct. The diagnosis is typically made
uncommonly, inferior STEMI presents with nausea and vagal when normal coronary arteries and the distinctive anteroapi-
symptoms rather than chest pain. Silent infarction may occur cal wall motion abnormality (Fig. 39.1) are seen at the time of
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404 Section III: Cardiovascular Problems and Coronary Care

A B

FIGURE 39.1. Representative contrast ventriculogram from a patient with Tako-Tsubo cardiomyopathy,
demonstrating an anteroapical wall motion abnormality. The ventriculogram in Panel A was obtained at
end diastole and in Panel B at end systole. [From the Libyan J Med, AOP: 070707, published July 19,
2007.]

emergent cardiac catheterization. In contrast to acute MI, car- to hospital arrival has provided an opportunity for a major
diac enzymes usually elevate only modestly and the left ven- enhancement in systems for STEMI care.
tricular (LV) functional abnormalities tend to be transient. The ST-segment elevation of acute MI must be distinguished
The pathophysiology of this syndrome is thought to be due from that due to pericarditis or even the normal early repolar-
to catecholamine-mediated myocardial stunning. ization variant. Ischemic ST-segment elevation typically has a
convex configuration, is limited to selected ECG leads, and is
often associated with reciprocal ST-segment depression (Fig.
Electrocardiogram 39.2). Pericarditis, on the other hand, is typically associated
with diffuse ST-segment elevation and depression of the PR
Performance of the 12-lead ECG in the prehospital setting sig- segment (Fig. 39.3). The contour of the elevated ST segment in
nificantly reduces time to reperfusion and shows a strong trend pericarditis and early repolarization variant is typically concave
toward reducing mortality [5]. Because only about 25% of pa- (upward sloping), in contrast to that seen with myocardial in-
tients with STEMI transported by emergency medical services jury. Reversible ischemic ST-segment elevation is also seen with
in the United States receive a prehospital ECG, this represents coronary vasospasm (Prinzmetals variant angina).
an important target for improvement [5]. The ability to trans- A new (or presumed new) left bundle branch block (LBBB)
mit the 12-lead ECG and activate a STEMI care team prior in a patient with ischemic chest discomfort suggests a large

I aVR V1 V4

II aVL V2 V5

III aVF V3 V6

II

FIGURE 39.2. Inferoposterior ST elevation MI complicated by complete heart block.


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Chapter 39: ST-Segment Elevation Myocardial Infarction 405

FIGURE 39.3. ECG changes characteristic of pericarditis. Concave (upsloping) ST-segment elevation is
seen diffusely, together with PR-segment depression. Importantly, T-waves are essentially normal, another
distinguishing feature from ST elevation MI.

anterior infarction, and is also an indication for reperfusion actually increase, with an earlier peak and more rapid fall in
therapy. A LBBB of unknown age, however, presents a biomarker levels.
diagnostic dilemma, because many of these patients do not Information from the patients clinical presentation and
have ongoing transmural myocardial ischemia. Here, emer- physical examination are also very valuable for assessing the
gent echocardiography (to look for an anterior wall motion patients prognosis. Evidence for heart failure or hemodynamic
abnormality); bedside testing of serum cardiac markers, such stress at the time of presentation is weighted heavily in this as-
as myoglobin, CKMB, or troponin; and even emergent cardiac sessment. For example, it is possible to use the patients age
catheterization should be considered. It should be emphasized and vital signs at presentation to rapidly and accurately obtain
that an acute STEMI leading to LBBB requires a very large a preliminary estimate of short-term survival [11]. Anterior in-
ischemic territory, and would not be expected to be a subtle farct location, delays to therapy, and information regarding
clinical event. In patients with a preexisting LBBB, no ECG cri- medical comorbidity all offer additional prognostic informa-
teria are sufficiently sensitive and specific to diagnose acute MI tion [12]. As such, several tools that integrate age, the physical
[6], so alternative methods are needed to make the diagnosis. examination, the ECG, and other clinical parameters such as
serum creatinine provide very strong discrimination of short-
and long-term mortality risk, and may be implemented using
either simple bedside calculation [12,13], handheld devices, or
Cardiac Biomarkers and Other web-based tools [14,15] (Fig. 39.4).
Tools for Risk Assessment
Cardiac biomarkers of necrosis are considerably more impor-
tant in the initial diagnosis of NSTEMI than they are in the REPERFUSION THERAPY
diagnosis of STEMI. For patients with STEMI, cardiac marker
Rapid provision of reperfusion therapy is the primary treat-
measurements are used to confirm the diagnosis in patients with
ment objective in patients presenting with STEMI. The man-
equivocal electrocardiographic changes, to help gauge prog-
aging clinician may choose between two principal reperfusion
nosis, and to estimate the likelihood of successful reperfusion
strategies: pharmacologic reperfusion versus primary percuta-
therapy. Cardiac markers also provide prognostic information.
neous coronary intervention (PCI). This decision may be based
Patients with an elevated myoglobin, troponin, or B-type na-
on institutional resources, as well as patient factors as discussed
triuretic peptide level prior to initiation of reperfusion therapy
in this section.
are at higher risk for death and congestive heart failure (CHF),
even after accounting for baseline variables such as infarct lo-
cation and time to treatment [79]. When combined with sub-
sequent measures of the efficacy of reperfusion therapy, such The Evolving Definition
as the degree of ST-segment resolution, an accurate assessment of Optimal Reperfusion
of prognosis can be made [8]. Although the rate of rise of car-
diac biomarkers (particularly myoglobin) can be used to help Early successful coronary reperfusion limits infarct size and
determine which patients have had successful or unsuccessful improves LV dysfunction and survival. These benefits are due
reperfusion [10], the clinical role of biomarker testing for reper- at least in part to the early restoration of antegrade flow in the
fusion assessment is limited. The peak levels of troponin, CK, infarct-related artery (IRA). In a retrospective analysis of six
or CKMB provide a crude estimation of infarct size. It should angiographic trials of different fibrinolytic regimens, patients
be noted that with successful reperfusion, although the total who achieved normal (TIMI grade 3) antegrade flow in the IRA
amount of biomarker released is reduced, the peak value may had a 30-day mortality rate of 3.6%, versus 6.6% in patients
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406 Section III: Cardiovascular Problems and Coronary Care

60
Age 65-74 / 75 2 / 3 points
DM/HTN or angina 1 point FIGURE 39.4. TIMI risk score for STEMI: a sim-
50 SBP <100 mm Hg 3 points ple, bedside, clinical tool for predicting 30-day mor-
HR >100 bpm 2 points tality. At the high end, a score of more than 5 iden-
Killip II -IV 2 points tified 12% of patients with a mortality risk at least
Weight <67 kg 1 point twofold higher than the mean for the population.
Mortality (%)

40
Anterior STE or LBBB 1 point In contrast, the 12% of patients with a risk score
Time to Rx > 4 h 1 point 32.0 of zero had a mortality rate of less than 1%. Dis-
30 criminating among the lower risk groups, nearly
Risk Score = Total (0-14 points)
24.0 two-thirds of the population had risk scores of 0
21.0 to 3 with a 5.3-fold gradient in mortality over
20 this range where smaller differences in absolute risk
15.0 may have clinical impact. h/o, history of; HTN, hy-
12.0 pertension; LBBB, left bundle branch block; STE,
10 6.5 ST-segment elevation; TIMI, Thrombosis in Myocar-
3.9 dial Infarction. [Adapted from Morrow DA, Antman
0.7 1.3 1.9 EM, Charlesworth A, et al: TIMI risk score for
0 ST-elevation myocardial infarction: a convenient,
bedside, clinical score for risk assessment at presen-
Risk Score: 0 1 2 3 4 5 6 7 8 >8 tation: an intravenous nPA for treatment of infarct-
ing myocardium early II trial substudy. Circulation
% at risk: 12 22 16 16 14 9 6 3 2 1 102(17):20312037, 2000.]

with slow (TIMI grade 2) antegrade flow, and 9.5% in patients assessed with cardiac magnetic resonance imaging also corre-
with an occluded artery (TIMI grade 0 or 1 flow) [16]. lates with higher mortality risk. Microvascular dysfunction is
Even among patients who achieve normal (TIMI grade 3) thought to occur in the setting of MI as a result of distal em-
epicardial blood flow in the IRA after reperfusion therapy, how- bolization of microthrombi, tissue inflammation from myocyte
ever, tissue-level perfusion may be inadequate. Using a number necrosis, and arteriolar spasm caused by tissue injury.
of different diagnostic tools (Table 39.2), investigators have Perhaps the most clinically relevant measure of tissue perfu-
demonstrated that measures of tissue and microvascular per- sion is a simple bedside assessment of the degree of resolution
fusion provide prognostic information that is independent of of ST-segment elevation on the 12-lead ECG. Greater degrees
TIMI flow grade [17] (Fig. 39.5). For example, Ito and col- of ST-segment resolution are associated with a higher proba-
leagues, using myocardial contrast echocardiography, found bility of achieving a patent IRA and TIMI grade 3 flow [19].
impaired tissue and microvascular perfusion in approximately Furthermore, patients who have normal epicardial blood flow,
one-third of patients with TIMI grade 3 blood flow after pri- but persistence of ST-segment elevation on the 12-lead ECG,
mary PCI: these patients were at increased risk for the develop- have been shown to have abnormal tissue and microvascular
ment of CHF and death [18]. Impaired microvascular perfusion perfusion using a variety of specific imaging modalities such
as contrast echocardiography and nuclear SPECT perfusion
imaging [20,21]. In addition, persistent ST-segment elevation
TA B L E 3 9 . 2 has been shown to predict poor recovery of infarct zone wall
motion and the clinical endpoints of death and heart failure
DIAGNOSTIC TOOLS USED TO EVALUATE TISSUE [22]. As a result, ST-segment resolution appears to integrate
AND MICROVASCULAR PERFUSION IN PATIENTS epicardial and myocardial (microvascular) reperfusion, and as
WITH ST ELEVATION MIa such may actually provide a more clinically useful assessment
of reperfusion than coronary angiography [23].
Finding suggestive of
Technique microvascular injury

Myocardial contrast Absence of microbubble contrast Time to Reperfusion


echocardiography uptake in the infarct zone
Doppler flow wire Abnormal coronary flow reserve; Regardless of the choice of reperfusion strategy, several com-
systolic reversal of coronary flow mon themes are evident. First, the benefits of reperfusion
PET scanning Impaired regional myocardial blood therapy are time dependent. Patients who receive fibrinolytic
flow as measured with 13 NH3 therapy within 1 hour from the onset of chest pain have an
Nuclear SPECT Absence of tracer uptake into infarct approximately 50% reduction in mortality, whereas those pre-
imaging zone senting more than 12 hours after onset of symptoms derive lit-
Contrast angiography Abnormal myocardial blush, with tle, if any, benefit. For each hour earlier that a patient is treated,
failure to opacify myocardium or there is an absolute 1% decrease in mortality [24]. Similarly,
prolonged dye washout from for primary PCI, the door-to-balloon time has been shown
myocardium to be directly correlated with clinical benefit [25].
MRI Hypoenhancement of infarct zone
following gadolinium contrast
injection
ECG Failure to resolve ST-segment
Fibrinolytic Therapy
elevation
The use of fibrinolytic therapy worldwide has decreased sub-
a
Assumes that the epicardial infarct artery is patent. These techniques stantially. Nevertheless, fibrinolytic therapy remains the pri-
can be presumed to reflect microvascular and tissue perfusion only mary approach to reperfusion therapy in some countries and
when the infarct artery has been successfully recanalized. in some regions in the United States where there is no access to
experienced centers for timely primary PCI.
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Chapter 39: ST-Segment Elevation Myocardial Infarction 407

9
8 p = 0.05 7.0%
Mortality (%)

7
6
5
4
3.7%
3
2
1 FIGURE 39.5. Relationship between
n = 487 n = 328 epicardial perfusion, myocardial per-
0
fusion, and mortality after fibrinolytic
Epicardial TIMI Grade 3 Flow Epicardial TIMI Grade 2 / 1 / 0 Flow therapy in the TIMI 10B trial. Myocar-
dial perfusion was assessed using the
9 5 way p = 0.007 TIMI Myocardial Perfusion Grade,
8 7.5% which assesses the degree of microvas-
Mortality (%)

cular blush seen on the routine coro-


7
nary angiogram. This study found that
6
5.4% myocardial perfusion was significantly
5
4.7% associated with mortality independent
of epicardial blood flow; using these
4 2.9% two measures together provided in-
3
cremental risk prediction. [Adapted
2 from Gibson CM, Cannon CP, Mur-
0.7% phy SA, et al; for the TIMI Study
1 n = 64 n = 226
0 n = 136 n = 34 n = 279 Group: The relationship of the TIMI
Myocardial Myocardial Myocardial Myocardial Myocardial Myocardial Perfusion Grade to mor-
Perfusion Perfusion Perfusion Perfusion Perfusion tality after thrombolytic administra-
Grade 3 Grade 2 Grades 0/1 Grade 3 Grades 2/1/0 tion. Circulation 101:125130, 2000.]

Placebo-controlled trials using streptokinase, anistreplase efficacy and bleeding risk to accelerated tPA in the GUSTO III
(APSAC), and tissue plasminogen activator (tPA) established a trial [26]. In the ASSENT II trial, tenecteplase (TNK-tPA)a
clear benefit of fibrinolytic therapy for patients with STEMI. single-bolus agentwas shown to be equivalent to tPA in terms
The Fibrinolytic Therapy Trialists overview of all the large of mortality and intracranial hemorrhage (ICH), but was asso-
placebo-controlled studies reported a 2.6% absolute reduction ciated with a lower rate of noncerebral bleeding complications
in mortality for patients with STEMI treated within the first 12 [27]. The safety advantage of this agent may be due to its in-
hours after the onset of symptoms [24]. This benefit has been creased fibrin specificity and the fact that the dose is adjusted
shown to persist through 10 years of follow-up. Highlights of for body weight.
differences in dosing, pharmacokinetics, recanalization rates, Although the bolus fibrinolytic agents have not been demon-
and cost between agents are shown in Table 39.3. strated in placebo-controlled trials to reduce mortality or ICH,
Several mutant forms of tPA have been developed that have they are easier to use and have largely replaced tPA for this
a prolonged half-life (to allow bolus administration), as well reason in the United States. Tenecteplase appears to offer a
as increased fibrin specificity and resistance to endogenous in- modest advantage in safety over other agents. Readministra-
hibitors of plasminogen, such as PAI-1. Bolus administration tion of streptokinase or anistreplase should be avoided for at
may minimize the risk for dosing errors, decrease door to nee- least 4 years (preferably indefinitely) because potentially neu-
dle time, and allow for prehospital administration. Reteplase tralizing antibodies may develop and because anaphylaxis can
(rPA) is a double-bolus agent that was shown to have similar occur on reexposure to these drugs.

TA B L E 3 9 . 3
THROMBOLYTIC AGENTS IN CURRENT CLINICAL USE

Alteplase Reteplase Tenecteplase Streptokinase

Fibrin selective +++ ++ ++++


Half-life 5 min 14 min 17 min 20 min
Dose 15 mg bolus; then 0.75 mg/kg Two 10 unit bolus 0.53 mg/kg as a 1.5 million units
over 30 min; then 0.5 mg/kg doses given single bolus over 3060 min
over 60 min (max 100 mg 30 min apart
total dose)
Weight adjusted Partial No Yes No
Adjunctive heparin Yes Yes Yes Probably
Possible allergy No No No Yes
TIMI grade 2 or 3 flow (90 min) 80% 80% 80% 60%
TIMI grade 3 flow (90 min) 55%60% 60% 55%65% 32%
Efficacy vs. tPA NA Similar Equivalent 1% mortality
Safety NA Similar Similar ICH ICH
non-ICH bleeding overall bleeding
Cost +++ +++ +++ +
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408 Section III: Cardiovascular Problems and Coronary Care

TA B L E 3 9 . 4
CONTRAINDICATIONS TO FIBRINOLYTIC THERAPY

Absolute contraindications Relative contraindications

Any prior intracranial Blood pressure >180/110a


hemorrhage
Stoke within past year Any prior stroke or TIA
Recent head trauma Known bleeding diathesis
Known brain tumor Proliferative diabetic
retinopathy
Active internal bleeding Prolonged CPR
Suspected aortic dissection Pregnancy
Major surgery or trauma
within 2 wk

CPR, cardiopulmonary resuscitation; TIA, transient ischemic attack.


a
Prior recommendations have considered only a sustained blood
pressure >180/110 a relative contraindication; however, even a single
blood pressure greater than this threshold is associated with an
increased risk for intracranial hemorrhage.
FIGURE 39.6. Limitations of current fibrinolytic regimens. [From
Lincoff AM, Topol EJ: Illusion of reperfusion. Does anyone achieve
optimal reperfusion during acute myocardial infarction? Circulation
Current Guidelines for Fibrinolysis 87:17921805, 1993.]

Fibrinolytic therapy is indicated as an option for reperfusion


therapy in patients presenting within 12 hours of symptom critical component of the white portion of the arterial throm-
onset if they have ST-segment elevation or new LBBB and no bus. Paradoxically, fibrinolytic agents directly and indirectly
contraindications to lytic therapy (Table 39.4). Patients who promote platelet activation [31], and activated platelets them-
are older than 75 years of age, those who present more than selves contribute to fibrinolytic resistance by secreting PAI-1
12 to 24 hours after the onset of acute MI, and those who are and promoting clot retraction, thereby limiting penetration of
hypertensive but present with high-risk MI have a less favorable the fibrinolytic agent into the thrombus. As a result of these
balance of risk and potential benefit, but may be considered for observations, it was hypothesized that potent platelet inhibi-
treatment with a fibrinolytic therapy when primary PCI is not tion with a GP IIb/IIIa inhibitor might augment the efficacy of
available. Patients should not be given fibrinolytic therapy if fibrinolytic therapy.
the time to treatment is longer than 24 hours or if they present Although a series of phase II studies comparing standard
only with ST-segment depression [28]. fibrinolytic therapy with various combinations of GP IIb/IIIa
inhibitors and reduced doses of fibrinolytic agents suggested
improved TIMI flow grade and ST-segment resolution with
Limitations of Fibrinolytic Therapy the combination regimens [3235], definitive phase III trials
revealed no convincing improvement in outcomes and an in-
Current fibrinolytic regimens achieve patency (TIMI grade 2 or crease in ICH in the elderly with combination regimens [36,37].
3 flow) in approximately 80% of patients, but complete reper- Thus, despite initial promise, data do not support the use of
fusion (TIMI grade 3 flow) in only 50% to 60% of cases. In ad- GP IIb/IIIa inhibitor/fibrinolytic combinations as the primary
dition, as noted previously in the chapter, approximately one- reperfusion strategy for treatment of STEMI.
third of patients with successful epicardial reperfusion have
inadequate myocardial and microvascular reperfusion [18]. Fi-
nally, even after successful fibrinolysis, a 10% to 20% risk of Rescue Percutaneous Coronary Intervention
reocclusion is present. Reocclusion and reinfarction are asso-
ciated with a two- to threefold increase in mortality [29,30] Because failure of fibrinolytic therapy is associated with high
(Fig. 39.6). rates of morbidity and mortality, rescue PCI is frequently
Bleeding is the most common complication of fibrinolytic performed in such patients. Data to support rescue PCI in pa-
therapy. Major hemorrhage occurs in 5% to 15% of patients. tients with an occluded infarct artery are limited, as tools to
ICH is the most devastating of the bleeding complications, diagnose failed reperfusion are only modestly effective, and
causing death in the majority of patients affected and almost clinical trials evaluating rescue PCI have enrolled very slowly.
universal disability in survivors. In major clinical trials, ICH In the MERLIN trial, 307 patients with ECG evidence of failed
has occurred in 0.5% to 0.9% of patients, but in clinical prac- reperfusion (ST-segment resolution <50% measured 60 min-
tice, where patient selection is less rigorous, rates are higher. utes after fibrinolytic therapy) were randomized to rescue PCI
Patients at particularly high risk for ICH include the elderly or conservative therapy. Rescue PCI was performed an aver-
(particularly elderly females), patients with low body weight, age of approximately 90 minutes after the qualifying ECG and
and those who receive excessive doses of heparin. was associated with a 26% reduction in the composite end-
point of death, reinfarction, stroke, heart failure, and revascu-
larization at 30 days. However, mortality was not significantly
Combination Therapy with a GP IIb/IIIa reduced. The most recent study performed was the REACT
Inhibitor and Reduced-Dose Fibrinolytic trial, in which 427 patients with ECG evidence of failed fibri-
nolysis at 90 minutes were randomized to repeat fibrinolysis,
Standard fibrinolytic therapy is directed at the fibrin-rich red conservative treatment, or rescue PCI. No benefit was observed
portion of the coronary thrombus. Activated platelets are the for repeat fibrinolysis, but rescue PCI reduced the primary
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Chapter 39: ST-Segment Elevation Myocardial Infarction 409

endpoint of death, reinfarction, stroke, or severe heart failure generally preferred for patients presenting within 12 hours of
at 6 months by 53%. Mortality was also reduced from 12.8% symptom onset unless contraindications are present [28].
in the conservative therapy arm to 6.2% in the rescue PCI arm. Advances in PCI technology have been rapidly translated
We recommend urgent catheterization and PCI for all patients from elective to emergent PCI. Compared with primary PTCA,
with persistent ST-segment elevation and ongoing chest pain primary stenting is associated with similar rates of death and
90 minutes after the administration of reperfusion therapy, un- reinfarction, but lower subsequent target vessel revasculariza-
less they are at particularly low risk for complications (i.e., tion rates [40,41]. Initial fears about stent thrombosis when
a young patient with an uncomplicated inferior MI). For pa- drug-eluting stents (DES) were placed in the setting of STEMI
tients who are pain free, but in whom the ST segments remain have not been realized, and recent studies demonstrate that the
elevated, urgent catheterization should also be strongly con- advantages of DES over bare metal stents (BMS) with regard
sidered, particularly if the patient has high-risk features, such to in-stent restenosis and target vessel revascularization extend
as older age, anterior location of infarction, diabetes, or prior to patients with STEMI [42,43]. One logistical issue merits
CAD. comment regarding stent choice. It may be difficult in the set-
ting of an evolving STEMI to determine whether a patient is a
good candidate for at least 1 year of uninterrupted aspirin and
thienopyridine therapy; a BMS would be preferred in situations
Primary Percutaneous where the clinician cannot make this determination.
Coronary Intervention Because of the large thrombus burden in STEMI, distal em-
bolization at the time of PCI is common and may cause ad-
In centers with adequate resources, experienced operators, and ditional tissue and microvascular injury. Strategies to prevent
an institutional commitment to programmatic excellence, im- distal embolization using embolic protection devices, which
mediate or primary PCI has become the preferred reperfu- are commonly used when PCI is performed in saphenous vein
sion method for patients with STEMI. Randomized trials per- grafts, cause delays in reperfusion and do not appear to im-
formed in both referral centers and experienced community prove outcomes when STEMI is due to native vessel obstruc-
hospitals have shown that primary PCI reduces the likelihood tion. In contrast, a simpler strategy of thrombus extraction
of death or MI when compared to fibrinolytic therapy [38]. has yielded very promising results. In a randomized trial of
Moreover, rates of major bleeding and stroke are also signifi- 1,071 patients with STEMI, manual thrombus aspiration be-
cantly lower with primary PCI than with fibrinolytic therapy fore PCI was demonstrated to improve TIMI myocardial perfu-
(Fig. 39.7). The relative benefits of primary PCI are greatest in sion grade and ST-segment resolution ( p < 0.001) [44], as well
patients at highest risk, including those with cardiogenic shock, as 1-year mortality (3.6% vs. 6.7%; p = 0.02) [45]. Aspiration
right ventricular infarction, large anterior MI, and increased thrombectomy is a reasonable option for patients undergoing
age (due partly to an increased ICH rate with fibrinolytic ther- primary PCI, particularly in patients with large thrombus bur-
apy). However, as with fibrinolytic therapy, rapid time to treat- den and shorter ischemic times [46].
ment is paramount to success [25]. In addition, while operator
and institutional experience are critical to realize the full ben-
efit of primary PCI, excellent results with primary PCI have
been demonstrated in well-trained community hospitals with- Performance Improvement Measures to
out on-site cardiac surgery [39]. Current ACC/AHA guidelines Improve Door-to-Balloon Times
recommend primary PCI over fibrinolytic therapy when it can
be performed by experienced operators in experienced centers Considerable attention has been focused on improving door-
within 90 minutes of presentation. When the door-to-balloon to-balloon times. A study by Bradley et al. [47] identified
time is expected to be longer than 90 minutes, fibrinolysis is key strategies that discriminated hospitals with shorter versus
longer door-to-balloon times (Table 39.5). Most of these strate-
gies have been adopted by the Door-to-Balloon (D2B) Alliance,
a quality improvement initiative aiming to achieve a door-to-
balloon time of 90 minutes or shorter for 75% or more of
nontransferred patients with STEMI [48].

TA B L E 3 9 . 5
PROCESS MEASURES TO IMPROVE
DOOR-TO-BALLOON TIMES

Emergency medicine physician activates the catheterization


laboratory
A single call to a central page operator activates the
catheterization laboratory
A prehospital ECG is used to activate the catheterization
laboratory activated while the patient is en route to the
hospital
Expectation that staff will arrive in the catheterization
laboratory within 2030 min (vs. >30 min) after being
paged
FIGURE 39.7. Short-term (4- to 6-week) outcomes from a meta-
An attending cardiologist is always on site (sleeps in
analysis of 23 randomized controlled trials comparing fibrinolytic ther-
apy with primary PCI. [Adapted from Keeley EC, Boura JA, Grines CL: hospital)
Primary angioplasty versus intravenous thrombolytic therapy for acute Real-time data feedback is provided to emergency
myocardial infarction: a quantitative review of 23 randomised trials. department and the catheterization laboratory staff
Lancet 361(9351):1320, 2003.]
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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410 Section III: Cardiovascular Problems and Coronary Care

Absolute Risk Difference in Death (%)


Transfer for Primary Percutaneous 15
Coronary Intervention
Although primary PCI is the preferred reperfusion option for 10
most patients who present to dedicated centers that can per-
form interventional procedures quickly and expertly, most pa- p = 0.006
5
tients with STEMI present to centers without primary PCI
readily available. In such cases, a decision must be made as 62 min Favors PCI
to whether immediate pharmacologic reperfusion therapy or 0
transfer for primary PCI (if possible) is the best alternative. Favors lysis
For patients in whom a rapid transfer is possible (time from
arrival at first hospital to balloon inflation <90 minutes or -5
0 20 40 60 80 100
PCI-associated delay <1 hour), transfer for primary PCI is
preferable. Unfortunately, data from the National Registry of PCI-Related Time Delay (Door-to-Balloon minus Door-to-Needle)
Myocardial Infarction (NRMI) through 2002 suggested that FIGURE 39.8. Metaregression evaluating the association between
only 4% of transferred patients underwent primary PCI with time delay associated with primary PCI and the absolute benefit of
a door-to-balloon time shorter than 90 minutes [49]. More primary PCI over fibrinolytic therapy. Circle sizes represent the sam-
recently, several referral centers or metropolitan areas have ple size of individual studies and the solid line represents the weighted
initiated regional transfer networks that have achieved door-to- metaregression. For every 10-minute delay to PCI, a 1% reduction
balloon times of 100 to 120 minutes [5052]. For patients with in the mortality difference of primary PCI versus lytics was observed.
contraindications to fibrinolytic therapy, evidence of failed fib- [Adapted from Nallamothu BK, Bates ER: Percutaneous coronary in-
rinolytic therapy, cardiogenic shock, or presentation more than tervention versus fibrinolytic therapy in acute myocardial infarction: is
12 hours after symptom onset, transfer to a center that can per- timing (almost) everything? Am J Cardiol 92(7):824826, 2003.]
form emergent PCI is indicated, even if delay times are longer
[53].
Several studies have compared strategies of routine transfer zation was reserved for patients with recurrent or provocable
of patients eligible for fibrinolytic therapy for primary PCI ver- ischemia [59,60]. Because these trials were published, dramatic
sus immediate fibrinolysis with or without transfer. Although advances in interventional cardiology have taken place, includ-
these studies have reported a lower incidence of adverse car- ing improvements in catheter and stent technology, careful at-
diac events among those randomized to transfer for primary tention to groin hemostasis, and improvements in adjunctive
PCI [54,55], generalizability of the results has been questioned antiplatelet and antithrombotic regimens; as a result, PCI can
as the very rapid transfer times in these studies are significantly be performed effectively and safely early after fibrinolytic ther-
shorter than those typically occur in the United States [49] and apy [61]. In addition, it is well known that patients who arrive
the rates of referral for rescue PCI were unusually low in these in the catheterization laboratory with a patent IRA prior to
trials. primary PCI, either due to spontaneous lysis or due to phar-
Subsequent analyses have helped to define the influence of macologic reperfusion, have an extraordinarily low risk for
symptom duration and transfer-related time delay on the ben- mortality [62].
efits of transfer for primary PCI. For example, among the 850 The term facilitated PCI has been coined to signify the ad-
patients enrolled in the PRAGUE-2 study, there was a signifi- ministration of a pharmacologic reperfusion regimen en route
cant and quantitatively large reduction in mortality (6.0% vs. to the cardiac catheterization laboratory for a planned pri-
15.3%; p < 0.02) among those who were randomized more mary PCI. A number of different pharmacologic pretreatment
than 3 hours after symptom onset. In contrast, there was no re- regimens have been proposed, including fibrinolytic agents
duction in mortality among patients presenting within 3 hours alone (at full or reduced dose), combinations of GP IIb/IIIa
[56]. Similar findings were observed in the CAPTIM trial in inhibitors and reduced-dose fibrinolytics, and GP IIb/IIIa in-
which the control arm received prehospital fibrinolytic [57]. hibitors alone. To date, the clinical trial results regarding facil-
A meta-analysis of randomized studies has suggested that if itated PCI using regimens that contain a fibrinolytic have been
the delay between immediate administration of a fibrinolytic disappointing: although surrogate measures of early reperfu-
and initiation of PCI is more than 1 hour, the pharmacologic sion are enhanced, no favorable efficacy outcomes have been
therapy becomes favored with respect to survival [58] (Fig. observed and bleeding rates are clearly increased [63,64].
39.8). These data form the basis of the recommendation in the Moreover, the usefulness of administration of a GP IIb/IIIa in-
AHA/ACC guidelines that fibrinolysis is generally preferred in hibitor alone prior to the arrival in the catheterization labora-
eligible patients who present within 3 hours of symptom onset, tory is uncertain [46,64].
and more than a 1-hour delay between fibrinolytic and primary An alternative pharmacoinvasive strategy that may be logis-
PCI is expected (Fig. 39.9). tically attractive for patients presenting to non-PCI centers is
to perform initial pharmacologic reperfusion therapy followed
by transfer for routine nonemergent coronary angiography and
Pharmacoinvasive Strategies revascularization if needed. This pathway has shown favorable
results in several relatively small studies [6567] and more re-
In light of the deleterious impact of delays to primary PCI on cently in the larger TRANSFER-AMI trial [68]. In TRANSFER-
myocardial salvage, an approach in which reperfusion is initi- AMI trial, 1,059 high-risk patients with STEMI presenting to
ated with a pharmacologic regimen and followed by angiog- hospitals without PCI capability received pharmacologic reper-
raphy and PCI is attractive, particularly among patients being fusion with a regimen that contained tenecteplase and were ran-
transferred for PCI. Nevertheless, there has been considerable domized to standard treatment on site or to immediate trans-
controversy as to the role of PCI after apparently successful fer and PCI within 6 hours after fibrinolysis. Interestingly, most
fibrinolytic therapy. In a series of trials performed in the late patients in the standard treatment arm underwent coronary an-
1980s, the TIMI investigators reported no benefit from rou- giography, but this was performed approximately 1 day later
tine application of an immediate or delayed invasive strategy, than in the transfer arm. The primary endpoint of death, MI,
compared to a more conservative strategy in which catheteri- recurrent ischemia, CHF, or cardiogenic shock within 30 days
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Chapter 39: ST-Segment Elevation Myocardial Infarction 411

STEMI patient who is a


candidate for reperfusion

Initially seen at a PCI Initially seen at a


capable facility non-PCI
capable facility
Initial treatment
with fibrinolytic
Send to Cath Lab for Transfer for primary therapy
primary PCI PCI (Class 1, LOE:A)
(Class I, LOE:A) (Class I, LOE:A)

HIGH RISK NOT HIGH RISK


Transfer to a PCI
Transfer to a PCI
Preparatory antithrombotic facility is
At PCI facility may be
(anticoagulant plus antiplatelet) reasonable for
facility, considered
early diagnostic
regimen evaluate (Class IIb,
angio & possible
for timing LOE:C),
PCI or CABG
of especially if
(Class IIa,
diagnostic ischemic
Diagnostic angio LOE:B),
angio symptoms
persist and
High-risk
failure to
patients as
reperfuse is
defined by 2007
suspected
STEMI Focused
Medical PCI CABG Update should
therapy only undergo cath
(Class 1: LOE B)

FIGURE 39.9. An algorithm for triage and transfer for primary PCI among patients with ST elevation MI.
[Adapted from Kushner FG, Hand M, Smith SC Jr, et al: 2009 Focused Updates: ACC/AHA Guidelines
for the Management of Patients With ST-Elevation Myocardial Infarction (updating the 2004 Guideline
and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (up-
dating the 2005 Guideline and 2007 Focused Update): a report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 120(22):2271
2306, 2009.]

was reduced from 17.2% in the standard treatment arm to initiated at an oral dose of 162 to 325 mg (preferably chewed)
11.0% in the early PCI arm (HR 0.64; p = 0.004). For pa- at the time the patient is first encountered by medical personnel
tients who present to hospitals without PCI capability and in in the field or emergency department. Following MI, lifelong
whom the door-to-balloon time is expected to be longer than therapy with aspirin is indicated to prevent recurrent cardiac
90 minutes, these data support a strategy of drip and ship, in events. Efficacy appears to be similar at all doses greater than
which standard pharmacologic reperfusion therapy is adminis- 75 mg, whereas bleeding risk clearly increases with higher as-
tered and the patient transferred for subsequent catheterization pirin dose. Thus, for most patients, an 81-mg dose of aspirin
and PCI. The timing of the catheterization and PCI remains is preferred for long-term secondary prevention [71].
controversial. Data from studies of facilitated PCI suggest that Clopidogrel is a thienopyridine derivative that inhibits the
very early PCI (i.e., within 2 hours) is not helpful and may be binding of ADP to the P2 Y12 receptor on the platelet surface,
harmful. However, the accumulated data described previously thereby decreasing platelet activation and aggregation. The
suggest favorable outcomes if the PCI is performed between 2 CLARITY trial compared clopidogrel (300-mg loading dose
and 24 hours after successful fibrinolytic therapy. An important followed by 75 mg per day) with placebo in 3,491 patients with
consideration may be the use of adequate anticoagulant and an- STEMI who were treated with standard pharmacologic reper-
tiplatelet therapy in the setting of the transient prothrombotic fusion including fibrinolytic therapy, aspirin, and heparin. The
state that may be initiated by the release of fibrin degradation primary composite endpoint of death, MI, or an occluded IRA
products during fibrinolysis. assessed at the time of protocol-mandated angiography (aver-
age 3 to 4 days) was reduced from 21.7% in the placebo arm
to 15.0% in the clopidogrel arm ( p < 0.001; Fig. 39.10). At 30
ADJUNCTIVE ANTIPLATELET AND days, the clinical composite of death, MI, or urgent revascular-
ization was reduced by 20% ( p = 0.03) [72]. The much larger
ANTITHROMBOTIC THERAPY COMMIT trial was performed in more than 45,000 patients
in China and was designed to evaluate the impact of adjunctive
Aspirin and Oral P2 Y12 Inhibitors clopidogrel (administered at 75 mg per day without a loading
dose) on death and major clinical events. Clopidogrel reduced
In patients with STEMI, aspirin decreases reocclusion and rein- death, reinfarction, or stroke by 9% and death alone by 7%,
farction rates by nearly 50% and mortality by approximately both of which were statistically significant [73]. In both these
25% [69]. The benefits of aspirin are comparable to those of trials, the combination of clopidogrel and aspirin showed no
fibrinolytic therapy, and when used together, aspirin and fibri- excess in bleeding compared to aspirin alone. Using the results
nolytic therapy provide additive benefit [70]. Aspirin should be of these two trials, clopidogrel should now routinely be added
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412 Section III: Cardiovascular Problems and Coronary Care

25
36%
36% 21.7 Odds
Odds Ratio
Ratio 0.64
0.64
Occluded artery or death/MI (%)

Odds
OddsReduction
Reduction (95%
(95% CI
CI0.53
0.530.76)
20
15.0 p = 0.00000036
P=0.00000036
15

FIGURE 39.10. Influence of clopidogrel on outcomes


10 in patients treated with fibrinolytic therapy for STEMI
in the CLARITY trial. The primary endpoint was an oc-
cluded infarct-related artery, or death or MI occurring
5 at or before the time of angiography 3 to 8 days af-
ter treatment. [Adapted from Sabatine MS, Cannon CP,
0.4 0.6 0.8 1.0 1.2 1.6 Gibson CM, et al: Addition of clopidogrel to aspirin and
n = 1,752 n = 1,739
0 fibrinolytic therapy for myocardial infarction with ST-
Clopidogrel Placebo segment elevation. N Engl J Med 352(12):11791189,
Clopidogrel Placebo better better 2005.]

to standard fibrinolytic regimens in patients younger than 75 60 mg followed by 10 mg daily is an option for patients treated
years [28]. with primary PCI, who do not have a contraindication on the
For patients undergoing primary PCI, an oral P2 Y12 recep- basis of specific risks for increased bleeding (including history
tor antagonist should be administered in addition to aspirin: a of known cerebrovascular disease) [46]. The TRITON-TIMI
loading dose followed by a minimum of 12 months of mainte- 38 trial enrolled 13,608 patients with ACS who were sched-
nance therapy is recommended for patients with STEMI receiv- uled to undergo PCI. Patients were randomized to prasugrel
ing a stent (BMS or DES) [46]. Presently available alternatives (60-mg loading dose and then 10 mg per day) or clopidogrel
include clopidogrel and prasugrel, a novel thienopyridine. (300-mg loading dose and then 75 mg per day): both the drugs
If clopidogrel is used, a loading dose of 300 to 600 mg were initiated at the time of PCI with no pretreatment given. In
should be given as early as possible before or at the time of the subgroup of patients with STEMI (n = 3,534), the primary
PCI [46]. Recently, higher loading dosages of clopidogrel have efficacy endpoint of CV death, MI, and stroke at a median
been evaluated in the CURRENT/OASIS 7 trial, which com- of 14.5 months was reduced from 12.4% in the clopidogrel
pared high-dose (600-mg loading dose, 150 mg per day for arm to 10.0% in the prasugrel arm (HR 0.79; p = 0.02). Stent
7 days, and then 75 mg per day) with standard-dose (300-mg thrombosis occurred in 2.4% patients randomized to clopido-
loading dose and then 75 mg per day) clopidogrel among grel versus 1.2% randomized to prasugrel ( p = 0.008; Table
24,769 patients with ACS, 17,232 (70%) of whom underwent 39.6). Importantly, in the STEMI subgroup, no significant dif-
PCI. The overall result of the trial was neutral. However, in ferences were noted in non-CABG bleeding between treatment
the subgroup of patients who underwent PCI, the higher dose arms [75].
clopidogrel strategy was associated with a lower rate of the Although the absence of clopidogrel pretreatment in
primary endpoint of cardiovascular (CV) death, MI, or stroke TRITON-TIMI 38 has important implications regarding the
at 30 days (4.5% vs. 3.9%; HR 0.85; p = 0.036). Risk reduc- interpretation of the efficacy advantage of prasugrel in the over-
tion was similar in the STEMI (n = 6,346) and UA/NSTEMI all trial, this issue is not relevant in patients with STEMI, who
(n = 10,996) subgroups; moreover, among patients with do not have time for pretreatment prior to primary PCI. Indeed,
STEMI, high-dose clopidogrel was associated with a lower risk patients with STEMI, who tend to be younger and at lower risk
for stent thrombosis (4.0% vs. 2.8%). The higher dose clopi- for bleeding than those with UA/NSTEMI, and who may ben-
dogrel regimen was also associated with a higher rate of major efit from more rapid and intensive early antiplatelet therapy,
bleeding (1.1% vs. 1.6%; p = 0.006) [74]. may be particularly attractive candidates for prasugrel.
Prasugrel is a novel thienopyridine that is more rapidly act- Ticagrelor is a novel direct acting and reversible oral antag-
ing, more potent, and associated with less response variability onist of the P2 Y12 receptor. This agent, which as of 2010 was
than clopidogrel. Prasugrel administered as a loading dose of not commercially available, provides more rapid onset (and

TA B L E 3 9 . 6
COMPARISON OF NOVEL ORAL ANTIPLATELET THERAPIES WITH CLOPIDOGREL: RESULTS FROM SUBGROUPS
WITH STEMI

TRITON-TIMI 38 PLATO

N = 3,534 N = 7,026

Endpoint Prasugrel Clopidogrel HR (95% CI) Ticagrelor Clopidogrel HR (95% CI)

CV death, MI, stroke 10.0% 12.4% 0.79 (0.650.97) 8.5% 10.1% 0.84 (0.720.98)
Stent thrombosisa 1.6% 2.8% 0.58 (0.360.93) 2.2% 2.9% 0.75 (0.590.95)
Non-CABG TIMI major bleedinga,b 2.4% 2.1% 1.11 (0.701.77) 4.5% 3.8% 1.19 (1.021.38)
a
The stent thrombosis and bleeding results from PLATO are from the entire study because the specific data for STEMI have not yet been reported.
b
TIMI major bleeding (non-CABG) was the primary bleeding endpoint in TRITON-TIMI 38 and was an additional bleeding endpoint in PLATO.
Note that endpoint assessment was at 15 months in TRITON-TIMI 38 and 12 months in PLATO
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Chapter 39: ST-Segment Elevation Myocardial Infarction 413

offset) of action and a more potent and predictable antiplatelet patients receiving streptokinase come from trials that evalu-
response than clopidogrel. It does not require activation by ated the low-molecular-weight heparins (LMWHs) reviparin
the cytochrome p450 system. In the PLATO trial [76], tica- and enoxaparin among patients receiving streptokinase com-
grelor (180-mg loading dose, 90 mg twice daily) was compared pared either to placebo (reviparin) or to UFH (enoxaparin)
to clopidogrel (300- to 600-mg loading dose, 75 mg daily) in [78,79]. These trials provide both definitive evidence for the
18,624 patients with ACS, 38% of whom had STEMI. At the clinical benefit of administering an antithrombin in combina-
end of the 12-month follow-up period, the primary endpoint tion with a fibrinolytic and strong support for their use in con-
of CV death, MI, and stroke occurred in 11.7% of subjects junction with streptokinase as well as the fibrin-specific agents.
in the clopidogrel arm versus 9.8% in the ticagrelor arm (HR LMWHs represent an attractive alternative to UFH for
0.84; 95% CI 0.77 to 0.92; p < 0.001). The risk reduction was patients receiving fibrinolytic therapy. Following a series of
similar for UA/NSTEMI (HR 0.83; 95% CI 0.74 to 0.93) and smaller studies that yielded promising results, the ExTRACT-
STEMI (HR 0.84; 95% CI 0.72 to 0.98; Table 39.6). Similar TIMI 25 trial randomized 20,506 patients treated with stan-
to the CURRENT/OASIS 7 and TRITON-TIMI 38 trials, stent dard fibrinolytic regimens to intravenous UFH for 48 hours or
thrombosis was reduced significantly with the more potent oral to enoxaparin. Enoxaparin was given as a 30-mg IV bolus fol-
antiplatelet regimen. Also consistent with prior studies, an in- lowed by 1 mg per kg every 12 hours until hospital discharge
crease in non-CABG major bleeding was observed in the tica- [79]. The bolus dose was eliminated and the maintenance dose
grelor arm (4.5% vs. 3.8%; p = 0.03); however, bleeding rates reduced to 0.75 mg per kg for patients older than 75 years, be-
following CABG were lower with ticagrelor, likely because of cause previous trials had suggested a higher risk of ICH among
the shorter half-life of the drug [76]. elderly patients with STEMI who received full-dose enoxaparin
Several notable findings were observed with ticagrelor in the [80]. The primary endpoint of death or reinfarction was re-
PLATO trial. First, a significant 21% relative risk reduction duced from 12.0% in the UFH arm to 9.9% in the enoxaparin
in vascular mortality and a 22% reduction in total mortality arm (RR 0.83; p < 0.001). Major bleeding occurred in 1.4% of
(5.9% vs. 4.5%; p < 0.001) were observed. This is notable UFH-treated patients versus 2.1% of those treated with enoxa-
as none of the thienopyridine trials demonstrated a mortality parin ( p < 0.001), but there was no significant difference in
reduction. In addition, several unique side effects have been ob- ICH, and the net clinical benefit (death/MI/major bleeding) fa-
served with ticagrelor, which are likely mediated by adenosine. vored enoxaparin.
These include transient dyspnea, which occurs in 10% to 15% Fondaparinux, a novel factor Xa inhibitor, was evaluated
of patients early after treatment initiation, but is not associated in the OASIS 6 trial, a complex trial that included patients
with heart failure and usually terminates within a week. Ven- treated with both fibrinolytic therapy and primary PCI, and
tricular pauses may also be triggered by ticagrelor early after also included patients with and without indications for UFH.
treatment initiation, but these also decrease in frequency over Although the rate of death or reinfarction was significantly re-
time, are rarely symptomatic, and have not required clinical duced by 21% with fondaparinux compared with placebo, no
intervention. difference was observed compared with UFH. No increase in
bleeding risk was seen with fondaparinux. Notably, the
OASIS 6 trial demonstrated a hazard associated with the use
GP IIb/IIIa Inhibitors of fondaparinux to support primary PCI [81].
The direct antithrombin agents have also been extensively
Although use of GP IIb/IIIa inhibitors in elective PCI has been studied as adjuncts to fibrinolytic therapy, but appear to of-
decreasing, these agents remain useful adjuncts to primary PCI fer no significant advantage over UFH when given with any
in patients with STEMI when heparin is the anticoagulant used. of the currently available fibrinolytic agents [8284]. Thus, of
In a meta-analysis involving 3,266 patients enrolled in four the currently available antithrombin agents, LMWH admin-
randomized trials comparing abciximab with placebo, patients istered for the duration of the hospitalization (up to 8 days)
receiving abciximab had a 46% reduction in 30-day death, re- has been shown to be superior to guidelines-based use of UFH.
infarction, and urgent target vessel revascularization compared Fondaparinux is superior to placebo and appears to provide
to those who received placebo [77]. Fewer data are available similar efficacy and safety to UFH. Observations from both
for the other GP IIb/IIIa inhibitors (tirofiban and eptifibatide) in ExTRACT-TIMI 25 and OASIS 6 indicate that more prolonged
the primary PCI setting. Current ACC/AHA guidelines recom- administration of an anticoagulant for the duration of the in-
mend selective use of any of these agents at the time of primary dex hospitalization is beneficial compared with administering
PCI (class IIa recommendation), for example, among patients UFH only for 48 hours. As such, present guidelines recom-
with a large thrombus burden or those who have not received mend that patients managed with fibrinolysis should receive
adequate thienopyridine loading [46]. anticoagulant therapy for a minimum of 48 hours and prefer-
ably for the duration of the hospitalization after STEMI, up
to 8 days [53]. Enoxaparin or fondaparinux are preferred over
UFH when administration of an anticoagulant for longer than
Antithrombin Therapies in Patients 48 hours is planned in patients with STEMI treated with a
Receiving Fibrinolytic Therapy fibrinolytic.

Using data from angiographic trials showing improved IRA


patency rates 5 to 7 days after treatment with intravenous
unfractionated heparin (UFH) and subsequent outcomes tri- Antithrombin Therapy as an
als with alternative anticoagulants, the AHA/ACC guidelines Adjunct to Primary PCI
recommend administration of an anticoagulant (UFH, enoxa-
parin, or fondaparinux) as adjunctive therapy in all patients Until recently, UFHadministered in combination with a GP
receiving pharmacologic reperfusion therapy with the fibrin- IIb/IIIa receptor antagonisthas served as the preferred ad-
specific agents alteplase, reteplase, or tenecteplase. For UFH, junctive regimen to support primary PCI for STEMI. In the
recommended dosing is a 60 U per kg bolus (maximum bolus HORIZONS-AMI trial [85], 3,602 patients undergoing pri-
of 4,000 U) plus an initial infusion of 12 U per kg per hour mary PCI for STEMI were randomized to standard care with
(with a maximum initial infusion rate of 1,000 U per hour) heparin plus a GP IIb/IIIa inhibitor or to bivalirudin (a direct-
for up to 48 hours. Data to support antithrombin therapy for acting antithrombin) alone. The primary outcome, which was
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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414 Section III: Cardiovascular Problems and Coronary Care

Net adverse clinical events 30-Day MACE


HR = 0.76 [0.63, 0.92] p = 0.005 Heparin + GPIIb/IIIa (n = 1,802)
8

9 8.3% UFH + GPIIb/IIIa Bivalirudin 7 Bivalirudin monotherapy (n = 1,800)


8 6
7 FIGURE 39.11. Results from the
5
6 5.5% 5.4% HORIZONS-AMI trial. Among
4.9% patients receiving primary PCI for
5 4
STEMI, randomization to bivalirudin,
%

3 Acute stent thrombosis


4 3.1% as compared to unfractionated heparin
1.3% vs 0.3%, p < 0.001 plus a GP IIb/IIIa inhibitor, reduced
3 2.1% 2
bleeding complications and mortality,
2 HR [95%CI] = 1.00 [0.75, 1.32] but was associated with an increase in
1
1 p = 0.98 early stent thrombosis. [Adapted from
0 0 Stone GW, Witzenbichler B, Guagliumi
0 5 10 15 20 25 30 G, et al: Bivalirudin during primary
Major MACE Mortality PCI in acute myocardial infarction.
bleeding Time in Days
N Engl J Med 358(21):22182230,
p < 0.001 p = 1.0 p = 0.048 2008.]

a composite of efficacy and safety endpoints at 30 days, was suggests that triple therapy is associated with substantially
significantly lower in the bivalirudin versus heparin/GP IIb/IIIa increased risks for bleeding. It may be expected that risks will
inhibitor arm (9.2% vs. 12.1%; RR 0.76; p = 0.005). This be even higher with combinations that include the newer and
was mediated by lower rate of major bleeding with bivalirudin more potent antiplatelet agents such as prasugrel and ticagrelor.
(4.9% vs. 8.3%; RR 0.60; p < 0.001) and similar rates of the As such, we recommend attempting to avoid altogether or to
ischemic outcomes. Total mortality (2.1% vs. 3.1%; p = 0.05) minimize the duration of triple therapy. Consideration should
and cardiac mortality (1.8% vs. 2.9%; p = 0.03) trended lower be given to using BMS instead of DES, which would allow the
in the bivalirudin arm (Fig. 39.11). One issue of some concern duration of clopidogrel to be reduced to 1 month. For patients
was an increased risk of stent thrombosis within the first 24 who require triple therapy, the INR should be maintained at
hours in the bivalirudin group. It is possible that this early risk the lowest end of the therapeutic range, aspirin dose should
for stent thrombosis may be mitigated by using higher loading be reduced to 81 mg, and GI prophylaxis with an H2 antag-
doses of clopidogrel [86] or by using more potent novel P2 Y12 onist, such as ranitidine, should be considered. For patients
inhibitors, such as prasugrel. Bivalirudin is a useful alternative with atrial fibrillation, a reevaluation of the risks of bleeding
to heparin in patients undergoing primary PCI [46]. and stroke (using a tool such as the CHADS2 score) should be
performed and the threshold to initiate or continue warfarin
should be higher among patients on aspirin and clopidogrel
[91].
Warfarin/Oral Anticoagulation
Warfarin monotherapy appears to be at least as effective as
aspirin for secondary prevention post-MI. There are several
ANTI-ISCHEMIC THERAPY
circumstances in which the benefit with warfarin therapy may
exceed that of aspirin. First, warfarin is superior to aspirin Beta-Blockers
in preventing systemic emboli in patients with atrial fibrilla-
tion. In addition, it reduces systemic emboli in patients with Beta-blockers were among the first therapeutic interventions
documented LV dysfunction following MI. Because there is a used to limit the size of acute MI. Previous trials that ex-
substantial risk of systemic embolization following a large an- cluded patients with heart failure, hypotension, or bradycardia
terior MI, even if thrombus is not visible on echocardiography, demonstrated that very early administration of a beta-blocker
many experts recommend 3 to 6 months of warfarin therapy decreases infarct size and prevents recurrent MI and death [92].
in these patients if they are suitable candidates for anticoag- The fact that beta-blockers were particularly effective in re-
ulation [53]. Studies have also evaluated the combination of ducing sudden death and reducing mortality among patients
warfarin and aspirin post-MI. Neither fixed-dose warfarin nor with complex ventricular ectopy at baseline suggests that beta-
low-dose warfarin titrated to an INR of approximately 1.5 to blockers exert much of their beneficial effect by reducing the
2.0 appears to be superior to monotherapy with either agent frequency and severity of arrhythmias [93]. In addition, they
alone, and the combination is associated with excess bleeding appear to significantly decrease the risk of cardiac rupture.
risk [87]. Several studies have shown that the combination of Data from the COMMIT trial in more than 45,000 patients,
aspirin and warfarin is effective in preventing reocclusion and however, failed to demonstrate benefit from a strategy of imme-
clinical events when the INR is maintained at a higher level diate intravenous metoprolol followed by 200 mg metoprolol
consistently [8890]. However, these findings are of question- daily on in-hospital outcomes, including death and MI. Al-
able significance in light of the results of the CLARITY and though early beta blockade reduced the risks of reinfarction
COMMIT trials, which have demonstrated similar benefit with and ventricular fibrillation (VF) compared to placebo, this was
a simpler regimen of aspirin and clopidogrel. Thus, warfarin counterbalanced by an increased risk of cardiogenic shock dur-
plus low-dose aspirin may be a good choice in patients who ing the first few days after admission [94]. Post-hoc analyses
have another indication for anticoagulation (such as atrial fib- indicate that this increased risk was predominantly among pa-
rillation or prosthetic valve), provided the bleeding risk is low tients with indicators of or risk factors for hemodynamic com-
and a warfarin clinic is available for very careful monitoring. promise. In addition, the outcome may have been influenced
An increasingly challenging scenario relates to the combina- by the high dose of metoprolol used in this study. ACC/AHA
tion of aspirin, clopidogrel, and warfarin. Emerging evidence guidelines now recommended that beta-blockers be initiated
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Chapter 39: ST-Segment Elevation Myocardial Infarction 415

orally, within the first 24 hours, once it has been determined ical trials does not support routine long-term nitrate therapy
that the hemodynamic status is stable and there is no evidence for patients with uncomplicated MI, it is reasonable to give in-
of heart failure. Parenteral beta-blockers should be used only travenous nitroglycerin for the first 24 to 48 hours in patients
if there is a clear indication such as ongoing chest pain or an with acute MI who have CHF, recurrent ischemia, or hyper-
atrial tachyarrhythmia with normal or elevated blood pressure tension. Intravenous therapy is preferred in the early phases of
[28]. MI due its immediate onset of action and ease of titration.
When given long term following MI, beta-blockers signifi-
cantly reduce the incidence of nonfatal reinfarction and mor-
tality, an effect that extends to most members of this class of
agents [93]. The CAPRICORN trial examined the incremen- Calcium Channel Blockers
tal effect of beta blockade to angiotensin-converting enzyme
(ACE) inhibition in post-MI in patients with LV dysfunction The calcium channel blockers in current use block the entry
but no clinical heart failure. Over a mean follow-up of 1.3 of calcium into cells via voltage-sensitive calcium channels. In
years, the composite of death and myocardial infarction was vascular smooth muscle cells, this causes coronary and periph-
reduced from 20% in the placebo arm to 14% in the carvedilol eral vasodilation, whereas in cardiac tissue, it leads to depres-
arm, a 29% relative reduction. On the basis of robust clinical sion of myocardial contractility, sinus rate, and atrioventricular
data and a very favorable cost-to-benefit ratio, long-term oral (AV) nodal conduction. The dihydropyridine calcium channel
beta blockade should be continued indefinitely following MI. antagonists, of which nifedipine is the prototype, cause coro-
nary and peripheral artery dilation without blocking sinus or
AV nodal function. As a result, the potential benefit of these
Angiotensin-Converting Enzyme Inhibitors agents is counterbalanced by reflex tachycardia. The short-
acting preparations of nifedipine, in particular, appear to be
ACE inhibitors are routinely used following STEMI to prevent dangerous in the setting of acute MI, as they may cause rapid
adverse LV chamber remodeling, a gradual process by which hemodynamic fluctuations. Sustained-release preparations of
the left ventricle assumes a more globular shape and dilates; nifedipine, on the other hand, can be used safely in combina-
remodeling is associated with an increased risk for CHF and tion with a beta-blocker. Amlodipine is a third-generation agent
death. A large overview of almost 100,000 patients found a that causes less reflex tachycardia than other dihydropyridines,
7% reduction in 30-day mortality when ACE inhibitors were but as with other calcium channel blockers, there is no docu-
given to all patients with acute MI, with most of the benefit mented benefit of this agent following MI, so it should only be
observed in the first week. The benefit was greatest in high- used in patients who remain hypertensive after full-dose beta
risk groups, such as those in Killip class II or III, those with LV blockade and ACE inhibition.
dysfunction, and those with an anterior MI [95]. In addition to Diltiazem and verapamil slow the heart rate and modestly
preventing remodeling and CHF, ACE inhibitors also prevent reduce myocardial contractility, thereby decreasing myocardial
recurrent ischemic events after MI [96]. As opposed to aspirin oxygen demand. Of the two agents, verapamil has greater nega-
and reperfusion therapy, it is not crucial to introduce the ACE tive inotropic and chronotropic effects. These agents have been
inhibitor in the hyperacute phase of acute MI. given to patients as secondary prevention after stabilization of
Angiotensin receptor blockers (ARBs) are effective alter- an index MI. A pooled analysis indicated that verapamil and
natives to ACE inhibitors in patients with LV dysfunction or diltiazem had no effect on mortality following acute MI, but
heart failure following acute MI, and provide similar long-term that they did significantly reduce the rate of reinfarction (6.0%
outcomes [97]. However, combination therapy with ACE in- vs. 7.5%; p < 0.01) [101]. Despite an overall neutral effect of
hibitors and ARBs is not effective post-MI [97]. Because of the these agents on mortality, among patients with depressed LV
larger evidence base and lower cost of ACE inhibitors, they function or evidence of CHF, mortality is increased in patients
are preferred over ARBs unless side effects to ACE inhibitors treated with diltiazem or verapamil.
develop. It should be emphasized that there have not been studies
Aldosterone antagonists should also be considered for use comparing the efficacy of verapamil or diltiazem to a beta-
in appropriate high-risk patients following STEMI, who are blocker. Beta-blockers consistently reduce both mortality and
receiving adequate doses of ACE inhibitors. In the EPHESUS reinfarction and should be recommended for all patients who
trial, which included patients with an LV ejection fraction can tolerate them. Verapamil or diltiazem may be a reason-
<40% following an MI and either heart failure symptoms or able alternative for patients who cannot tolerate a beta-blocker,
diabetes, eplerenone treatment (compared to placebo) was as- provided LV function is normal, but they should not be given
sociated with a 15% reduction in the risk for mortality [98]. routinely following MI.
Because of its much lower cost, spironolactone may be consid-
ered as an alternative to eplerenone. Aldosterone antagonists
should be avoided in patients with hyperkalemia or significant
renal dysfunction. ARRHYTHMIAS COMPLICATING
ST ELEVATION MYOCARDIAL
Nitrates INFARCTION (Table 39.7)
Nitrates dilate large coronary arteries and arterioles, periph-
eral veins, and to a lesser extent, peripheral arterioles. Ven- Ventricular Arrhythmias
odilation decreases preload, thus reducing both myocardial
oxygen demand and symptoms of pulmonary congestion that Ventricular tachycardia (VT) occurs frequently during the first
may complicate MI. The GISSI-3 [99] and ISIS-4 [100] tri- few days after MI, but does not appear to increase the risk for
als collectively enrolled almost 80,000 patients and evaluated subsequent mortality if the arrhythmia is rapidly terminated.
the role of long-term (4- to 6-week) nitrate therapy post-MI. VT occurring after 24 to 48 hours, however, is associated with a
Neither study found a significant reduction in mortality with marked increase in mortality. Monomorphic VT is usually due
nitrates, although the power to detect such a difference may to a reentrant focus around a scar, whereas polymorphic VT is
have been reduced because more than 50% of patients received more commonly a function of underlying ischemia, electrolyte
off-protocol nitrates. Although evidence from randomized clin- abnormalities, or drug effects.
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416 Section III: Cardiovascular Problems and Coronary Care

TA B L E 3 9 . 7
ELECTRICAL COMPLICATIONS OF ACUTE MI

Complication Prognosis Treatment

Ventricular tachycardia/fibrillation
Within first 2448 h Good Immediate cardioversion; amiodarone or lidocaine; beta-blockers
After 48 h Poor Immediate cardioversion; electrophysiology study/implantable defibrillator;
amiodarone
Sinus bradycardia Excellent Atropine for hypotension or symptoms
Second-degree heart block
Mobitz type I (Wenckebach) Excellent Atropine for hypotension or symptoms
Mobitz type II Guarded Temporary pacemaker
Complete heart block
Inferior MI Good Temporary pacemaker
Anterior MI Poor Temporary pacemaker followed by permanent pacemaker

VF is the primary mechanism of arrhythmic sudden death. ventricle. Thus, this arrhythmia is usually seen with inferior
In patients with acute MI, most episodes of VF occur early (<4 MI. If the heart rate is extremely low (<40 to 50) and is associ-
to 12 hours) after infarction. As with sustained VT, late VF oc- ated with hypotension, intravenous atropine should be given.
curs more frequently in patients with severe LV dysfunction or Mobitz type I (Wenckebach) second-degree AV block is also
CHF, and is a poor prognostic marker. Patients with VF, or sus- very common in patients with inferior wall MI, and may be due
tained VT associated with symptoms or hemodynamic compro- to ischemia or infarction of the AV node or to increased vagal
mise, should be cardioverted emergently. Underlying metabolic tone. The level of conduction block is usually located within
and electrolyte abnormalities must be corrected, and ongoing the AV node, and therefore the QRS complex is narrow and the
ischemia should be addressed. We aim to maintain the serum risk for progression to complete heart block is low. Atropine
potassium level to 4.5 mEq per L or greater and serum mag- should be reserved for patients with hypotension or symptoms,
nesium level 2 mEq per L or more. Intravenous amiodarone and temporary pacing is rarely required. Mobitz type II block
is a particularly effective antiarrhythmic agent in patients with is observed much less often than Mobitz type I block in acute
acute MI, because it lowers heart rate. Lidocaine remains an MI. As opposed to Mobitz type I block, Mobitz type II block
effective alternative if amiodarone is not tolerated or is un- is more frequently associated with anterior MI, an infranodal
successful in controlling the arrhythmia. Prophylactic use of lesion, and a wide QRS complex. Because Mobitz type II block
antiarrhythmic agents, other than beta-blockers, is not indi- can progress suddenly to complete heart block, a temporary
cated. pacemaker is indicated.
Although compete heart block may occur with either infe-
rior or anterior MI, the implications differ markedly depending
Bradyarrhythmias on the location of the infarct. With inferior MI, heart block of-
ten progresses from first-(or Wenckebach) to third-degree AV
The usual cause of bradycardia is increased vagal tone or is- block (see Fig. 39.2). The level of block is usually within or
chemia/infarction of conduction tissue. Sinus bradycardia is above the level of the AV node, the escape rhythm is often
typically due to irritation of cardiac vagal receptors, which are stable, and the effect is transient. Although temporary pacing
located most prominently on the inferior surface of the left is often indicated, a permanent pacemaker is rarely required.

TA B L E 3 9 . 8
SUMMARY OF ADVANCES IN MANAGING STEMI BASED ON RANDOMIZED CONTROLLED CLINICAL TRIALS

Performance of a prehospital ECG reduces reperfusion times in STEMI [5]


Fibrinolytic therapy reduces mortality vs. placebo if administered within 12 h of symptom onset, but is associated with a small
risk of intracranial hemorrhage [24]
Aspirin reduces mortality to a similar extent as fibrinolytics [70]
Primary PCI is superior to fibrinolytic therapy for patients who can be treated within 90 min of presentation in a high-volume
center [38]
Transfer to another facility for early nonemergent PCI should be considered following successful fibrinolytic therapy [68]
The addition of clopidogrel to aspirin, antithrombins, and fibrinolytic therapy reduces recurrent MI and mortality [72,73]
Prasugrel and ticagrelor represent alternatives to clopidogrel that reduce stent thrombosis and recurrent ischemic events, but at an
increased risk for bleeding [75,76]
Enoxaparin is superior to unfractionated heparin as an adjunct to fibrinolytic therapy, but is associated with slightly more
bleeding [79]
Beta-blockers improve long-term outcomes following STEMI, but may increase risk when given early to unstable patients [93,94]
ACE inhibitors prevent adverse remodeling after STEMI and reduce death and heart failure events [95]
Aldosterone antagonists reduce mortality in patients with LV dysfunction or heart failure following MI, but should be used in
caution in individuals with renal dysfunction [98]
Nitrates and calcium blockers are indicated in selected patients, but not routinely [100,101]
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Chapter 39: ST-Segment Elevation Myocardial Infarction 417

With anterior MI, complete heart block is usually a result of Although atrial fibrillation is usually transient, it is a marker
extensive infarction involving the bundle branches. The escape for increased morbidity and mortality, probably because it is
rhythm is usually unstable and the AV block permanent. Mor- associated with other adverse risk predictors such as LV dys-
tality is extremely high, and permanent pacing is almost always function and CHF. Management of supraventricular arrhyth-
required in survivors. mias in the setting of acute MI is similar to management in
other settings; however, there should be a lower threshold for
cardioversion and ventricular rate should be more aggressively
controlled (Table 39.8). Because of their beneficial effects in
Supraventricular Arrhythmias acute MI, beta-blockers are the agents of choice to control rate.
Diltiazem or verapamil may serve as alternatives in patients
Atrial fibrillation may occur in up to 15% of patients early after without significant CHF or LV dysfunction, whereas digoxin
MI, but atrial flutter and paroxysmal supraventricular tachy- should be reserved for patients with concomitant LV dysfunc-
cardia are not commonly seen. Ischemia itself rarely causes tion. Of the antiarrhythmic agents available, amiodarone is
atrial fibrillation, except in rare cases of atrial infarction: more safest in patients with recent MI, because it has a low risk for
common precipitants include heart failure and pericarditis. proarrhythmia.

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P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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CHAPTER 40 MECHANICAL COMPLICATIONS


OF MYOCARDIAL INFARCTION
ANNABEL A. CHEN-TOURNOUX AND MICHAEL A. FIFER

responding to regional wall motion abnormalities observed


PATHOPHYSIOLOGY with imaging modalities, such as echocardiography. Electro-
UNDERLYING MYOCARDIAL cardiogram (ECG) changes appear as well. Disruption of the
STUNNING AND ITS TIME cell membrane allows protein leakage out of the cell, pro-
ducing serologic evidence of myocyte injury. If blood flow is
COURSE FOLLOWING ISCHEMIA restored within 15 minutes of coronary occlusion, myocyte
AND REPERFUSION injury is reversible. Glycolysis ceases after approximately
40 minutes of severe ischemia, after which time injury becomes
Within 8 to 10 seconds after occlusion of an epicardial coro- irreversible and myocytes are not salvageable by reperfusion.
nary artery, myocardial oxygen supply is exhausted, resulting Even with earlier restoration of blood flow, however, a phe-
in a shift from aerobic to anaerobic metabolism. High-energy nomenon called myocardial stunning is observed.
phosphates (creatine phosphate and adenosine triphosphate First described in a dog model by Heyndrickx et al. [2] in
[ATP]) become depleted, whereas hydrogen ions, lactate, and 1975, stunning is defined as prolonged contractile dysfunction
other metabolic products accumulate, causing intracellular pH occurring after relief of a discrete episode or episodes of is-
to fall to 5.8 to 6.0 within 10 minutes of the onset of ischemia chemia. Importantly, the dysfunction associated with stunning
[1]. In addition, adenosine monophosphate (AMP) is degraded is completely reversible. By definition, myocardial perfusion
to adenosine, which diffuses into extracellular fluid, deplet- must be restored to normal or near normal to distinguish stun-
ing the intracellular adenine nucleotide pool. The ischemic ning from myocardial dysfunction due to continued ischemia
myocardium stretches instead of shortens during systole, cor- (hibernation). The severity and duration of stunning depend on
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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420 Section III: Cardiovascular Problems and Coronary Care

multiple factors, such as the extent of the original ischemic in- peutic decisions after MI. For example, LV ejection fraction
sult, the adequacy of restored flow, the presence of preexisting assessment for implantable cardiac defibrillator implantation
collateral vessels, and prior ischemic preconditioning. In gen- is generally deferred for at least 1 month following MI.
eral, the myocardium is stunned for a period longer than that
of the ischemic insult, often requiring hours to days to regain
function [3].
Although early restoration of flow is necessary for my- DIAGNOSIS, TREATMENT,
ocardial survival, reperfusion is also thought to underlie the AND OUTCOME OF SHOCK
pathogenesis of stunning, through the development of oxida-
tive stress and/or impaired calcium homeostasis [4]. In the first DUE TO LEFT VENTRICULAR
5 minutes of reperfusion, there is marked hyperemia, with a PUMP FAILURE
400% to 600% increase in flow, returning to the baseline level
after 15 to 20 minutes. Because levels of oxygen-free radicals Approximately 5% to 8% of patients with ST-segment eleva-
peak at 4 to 7 minutes, most of the free radical-induced injury tion MI (STEMI) and 2.5% of patients with nonST-segment
responsible for stunning is thought to occur in the initial mo- elevation MI develop cardiogenic shock (CS), the leading
ments following reperfusion. Blunted calcium transients and cause of death in patients hospitalized with MI (Table 40.1).
dysfunction of the ryanodine receptor and the sarcoplasmic CS is broadly defined as a state of end-organ hypoperfusion
reticulum calcium ATPase (SERCA-2), which would lead to due to cardiac failure. Clinical evidence of systemic hypop-
impaired myocyte excitationcontraction coupling, have also erfusion includes altered mental status, cold clammy skin,
been described following ischemiareperfusion. Other possible and oliguria. Hemodynamic parameters of CS include per-
mechanisms of reperfusion injury involved in myocardial stun- sistent (1 hour) hypotension (systolic blood pressure <80
ning include microvascular injury, endothelial cell dysfunction, to 90 mm Hg or mean arterial pressure 30 mm Hg lower
and activation of neutrophils, platelets, and the complement than baseline) not responsive to fluid or requiring inotropic
system. or vasopressor support to be maintained; low cardiac in-
Stunning is observed in clinical scenarios in which the heart dex (<1.8 L per minute per m2 without support or 2.0 to
is reperfused after transient ischemia, whether it be global, as 2.2 L per minute per m2 with support); and adequate or el-
with cardioplegia during cardiac surgery or transplant har- evated filling pressures (LV end-diastolic pressure >15 mm
vest, or regional, as with acute coronary syndromes, per- Hg or right ventricular [RV] end-diastolic pressure >10 to
cutaneous coronary interventions (PCI), or exercise-induced 15 mm Hg).
angina. In patients with coronary disease, stunning from re- In the absence of mechanical complications, the primary
peated episodes of demand ischemia may lead to chronic left insult in CS associated with MI is LV dysfunction due to exten-
ventricular (LV) dysfunction. sive infarction or ischemia. Although the magnitude of myocar-
Stunned, but viable, myocardium may be identified by dial insult does not correlate perfectly with the development of
echocardiographic, scintigraphic, and magnetic resonance CS [6], LV function nevertheless remains a prognostic factor in
imaging techniques [5]. Because ischemic myocytes have dif- CS [7].
ferent rates of injury and recovery, the timing of improve- The observation of normal to low systemic vascular resis-
ment after acute myocardial infarction (MI) is variable and tance among many patients with CS [8] suggests an important
often unpredictable. The major clinical implication of stun- role for inappropriate vasodilation in CS. Indeed, neurohor-
ning is that even brief periods of ischemia may be associated monal and cytokine abnormalities consistent with the systemic
with prolonged contractile dysfunction. Moreover, because this inflammatory response syndrome (SIRS) have been observed
dysfunction may be fully reversible, continued hemodynamic (Fig. 40.1) [6]. For example, cytokines with myocardial de-
support, with intra-aortic balloon counterpulsation and/or in- pressant activity, such as tumor necrosis factor (TNF)- and
otropic agents such as catecholamines or phosphodiesterase in- interleukin (IL)-6, increase over 24 to 72 hours after MI. MI
hibitors, may be indicated. Importantly, inotropic stimulation is also associated with abnormal NO metabolism [9] and in-
does not appear to worsen cell injury as long as the reperfused creased expression of inducible nitric oxide (NO) synthase; NO
artery is patent. Finally, myocardial stunning has implications excess causes vasodilation, depressed myocardial contractility,
for the timing of evaluation of LV function to guide thera- and interference with catecholamine action in CS. Despite the

TA B L E 4 0 . 1
NATIONAL REGISTRY OF MYOCARDIAL INFARCTION: ALL-CAUSE IN-HOSPITAL MORTALITY FOR PATIENTS
WITH ACUTE MYOCARDIAL INFARCTION

All MI patients No fibrinolytic therapy Fibrinolytic therapy


Cause of death (359,755) (%, n) (228,512) (%, n) (91,218) (%, n) p-value

Cardiogenic shock 3.5 (12,262) 4.1 (9,437) 2.3 (2,054) <0.001


Sudden cardiac arrest 2.9 (10,217) 3.7 (8,435) 1.5 (1,282) <0.001
Arrhythmias 1.5 (5,385) 1.9 (4,279) 0.9 (794) <0.001
Recurrent MI 0.7 (2,511) 0.9 (1,993) 0.4 (384) <0.001
EMD/myocardial rupture 0.8 (2,671) 0.8 (1,801) 0.7 (631) <0.001
Other cardiac 1.2 (4,221) 1.6 (3,556) 0.5 (468) <0.001
Overall mortality 10.4 (36,581) 12.9 (29,401) 5.9 (5,165) <0.001

EMD, electromechanical dissociation; MI, myocardial infarction.


Adapted from Becker RC, Gore JM, Lambrew C, et al: A composite view of cardiac rupture in the United States National Registry of Myocardial
Infarction. J Am Coll Cardiol 27:13211326, 1996, with permission.
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Chapter 40: Mechanical Complications of Myocardial Infarction 421

Myocardial infarction
Myocardial dysfunction
Systemic
Inflammatory Systolic Diastolic
response
syndrome
(IL-6, TNF- NO) LVEDP
Cardiac output Pulmonary congestion
Stroke volume

Hypotension Revascularization
Systemic
perfusion
Coronary
Perfusion pressure
Hypoxemia
Ischemia Relief of ischemia FIGURE 40.1. The cascade of physio-
logic events causing cardiogenic shock
after MI. IL-6, interleukin-6; LVEDP,
Compensatory Progressive left ventricular end-diastolic pressure;
vasoconstriction myocardial NO, nitric oxide; TNF-, tumor necro-
dysfunction sis factor-. [From Reynolds HR,
Hochman JS: Cardiogenic shock: cur-
Survival
rent concepts and improving outcomes.
DEATH with GOOD
Circulation 117:686697, 2008, with
QUALITY of LIFE
permission.]

growing recognition of SIRS associated with CS, therapies tar- In the SHOCK trial, lack of benefit with early revasculariza-
geting it remain unproven at this time. tion was noted for patients 75 years and older, possibly due to
Most cases of CS after acute coronary syndrome develop af- imbalances in baseline ejection fraction. Later studies, includ-
ter hospital presentation, with a median time of 10 to 11 hours ing the SHOCK registry [19], have shown a consistent benefit
(STEMI) and 76 hours (nonST-segment elevation MI) [10]. of revascularization in elderly patients selected for it. Thus, an
Predictors for CS have varied among different studies over time individualized approach weighing the risks and benefits of an
and include older age; prior MI, heart failure, diabetes, hyper- aggressive revascularization strategy is warranted for elderly
tension, or cerebrovascular disease; failed reperfusion; lower patients.
blood pressure and glomerular filtration rate; and higher heart Multivessel or left main disease is extremely common in
rate and serum glucose at presentation [6,11]. The only way patients with MI and CS. Coronary bypass surgery is recom-
to prevent CS appears to be very early reperfusion therapy for mended for extensive disease [18], although PCI of the infarct-
MI, whether through PCI or thrombolysis. related artery may be initially necessary to stabilize the patient.
Outcome in CS is closely related to the patency of the In addition to early revascularization, supportive therapy
infarct-related artery, in both retrospective analyses [12] and with inotropic agents and vasopressors (and avoidance of neg-
the prospective, randomized SHOCK (should we emergently ative inotropes and vasodilators) is critical. Diuretics or intra-
revascularize occluded coronaries in cardiogenic shock) trial. venous fluids may be required, depending on the intravascular
In this multicenter study, patients with acute MI and CS were volume status. Routine antithrombotic therapy for MI includes
randomly assigned to early (within 6 hours) percutaneous aspirin, heparin, and if immediate surgery is unlikely, clopi-
or surgical revascularization (152 patients) or initial medical dogrel. Oxygen supplementation is standard and mechanical
stabilization with subsequent revascularization permitted 54 ventilation may be necessary. Intensive insulin therapy is also
hours after randomization (150 patients) [13,14]. Fibrinolysis recommended in critically ill patients [18].
was recommended in the initial medical stabilization group, Hemodynamic management of CS may be guided by pul-
and intra-aortic balloon counterpulsation was recommended monary artery catheter monitoring and echocardiography.
in both treatment groups. Although there was an excess of Such monitoring also allows detection of mechanical compli-
death in the early revascularization group in the first 5 days, cations such as papillary muscle or ventricular septal rupture
likely related to procedural complications, early revasculariza- (VSR).
tion improved survival at 6 months and 1 year (46.7% vs. The principal mechanical therapy for CS is intra-aortic bal-
33.6%; p < 0.03), a benefit that remained stable at 3 and 6 loon counterpulsation, which augments coronary perfusion
years [15]. Although the benefit of revascularization increases and reduces cardiac afterload. For some patients who require
the earlier it is achieved, there is a survival benefit as long as 48 a bridge to recovery or subsequent transplantation, short-term
hours after MI and 18 hours after shock onset. The benefit of support may be offered in the form of LV assist device (LVAD)
early revascularization is similar for different subgroups (pa- or extracorporeal life support [20]. Comparisons of percuta-
tients with diabetes, women, patients with prior MI, early vs. neous LVAD to intra-aortic balloon counterpulsation (IABP)
late shock) and whether revascularization is achieved with PCI have shown similar mortality rates [2123].
or coronary artery bypass graft surgery [16]. Among patients Independent predictors of mortality in CS have varied in dif-
undergoing PCI, registry data indicate that stenting and gly- ferent studies over time, and include older age; history of hyper-
coprotein IIb/IIIa inhibitors are independently associated with tension, MI, or heart failure; lower blood pressure and worse
improved outcomes [17]. On the basis of these results, emer- renal function on presentation; failed reperfusion; and low LV
gency revascularization is recommended (class I) for patients ejection fraction [7,11,12,15]. Revascularization provides ben-
younger than 75 years with MI and CS, who are determined to efit at every level of risk, and registry studies in the United States
be suitable candidates [18]. If revascularization is not available, and Europe have indicated significant decline (approximately
fibrinolysis and intra-aortic balloon pump placement followed 60% to 48%) in mortality from CS in recent years, in parallel
by transfer to another facility is recommended. with increasing revascularization with PCI [11,24,25].
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422 Section III: Cardiovascular Problems and Coronary Care

counterpulsation may also be necessary. Pure -adrenergic ag-


RIGHT VENTRICULAR onists should be avoided because they may increase pulmonary
INFARCTION vascular resistance, to which the compromised RV is particu-
larly sensitive. Although tricuspid regurgitation usually remits
Right ventricular infarction (RVI) has been recognized as a dis- as RV function recovers, patients with papillary muscle rupture
tinct entity since the initial description of its unique clinical (PMR) or severe papillary muscle dysfunction and a dilated
and hemodynamic features in 1974 [26]. Most cases of RVI are annulus require surgical repair. Pericardiectomy and creation
due to proximal occlusion of a dominant right coronary artery, of atrial septal defects may be attempted in extreme cases of
and RVI has been described in up to 50% of patients with in- hemodynamic compromise.
ferior MI. (Very rarely, RVI may accompany anteroseptal MI Hemodynamic instability associated with RVI represents
due to a culprit left anterior descending artery lesion.) RVI only 5% of cases of CS complicating MI but portends a high
leads to RV hypokinesis and decreased delivery of LV preload in-hospital mortality, ranging from 23% in one report [35] to
across the pulmonary vasculature. In addition, acute RV di- 53% in the SHOCK trial registry [36]. Although RVI is as-
lation in the face of the restraining effects of the pericardium sociated with substantial in-hospital and first-year mortality,
leads to elevated intrapericardial pressure and leftward shift- patients surviving the acute insult generally have a good prog-
ing of the interventricular septum, further compromising LV nosis [37]. Most patients demonstrate recovery of RV function
filling [27]. in the weeks following RVI. The resilience of the RV after is-
Early recognition of RVI is crucial because of its implica- chemic injury has been attributed to the more favorable balance
tions for management and prognosis, so that involvement of between myocardial oxygen demand and coronary perfusion
the RV should be considered in all patients with inferior MI. as compared with the LV. The positive long-term course of pa-
Clinical indicators of RVI include hypotension in the setting tients after RVI highlights the importance of early diagnosis,
of clear lungs and elevated jugular venous pressure, although early reperfusion, and intensive hemodynamic support.
the latter may not be evident if the patient is relatively hy-
povolemic. Conversely, a volume-depleted patient may exhibit
sensitivity to preload reduction, such as with the use of nitrates MYOCARDIAL RUPTURE
or diuretics. Patients may also display evidence of interventric-
ular dependence, such as Kussmauls sign (distention of jugular Myocardial rupture is a rare, but immediately life-threatening,
veins during inspiration), more classically associated with peri- complication of MI, accounting for 10% to 15% of deaths.
cardial disease. Transmural necrosis or myocardial hemorrhage is found at the
Several ECG signs indicate RV involvement: ST-segment el- site of rupture. In the National Registry of Myocardial Infarc-
evation in lead 3 greater than in lead 2, ST-segment elevation tion, older age, female gender, and fibrinolysis were indepen-
in lead V1 , and ST-segment elevation in right-sided precordial dent predictors of myocardial rupture [38].
lead V4R , the latter being the most predictive [28] (Fig. 40.2). Myocardial rupture may occur despite a limited infarct area
These ECG abnormalities may resolve quickly (50% within and relatively preserved systolic function because of increased
10 hours) [29], underscoring the importance of obtaining a shear stress in the necrotic area or its ischemic boundaries. Rup-
right-sided ECG on presentation for all patients with inferior ture is possible at three sites: the ventricular free wall (85%),
MI. RVI may be associated with bradyarrhythmias (sinoatrial the ventricular septum (10%), or a papillary muscle (5%). The
or atrioventricular [AV] block) and tachyarrhythmias (atrial specific presentations and sequelae depend on the location of
fibrillation and ventricular tachyarrhythmias). Echocardiogra- the defect(s) (Table 40.2), but in all cases, prompt diagnosis
phy reveals RV dilation and hypokinesis and abnormal septal and definitive surgical therapy are critical.
motion, along with inferior LV hypokinesis, and possibly other
complications of RVI, such as tricuspid regurgitation, VSR, RV
mural thrombus and pulmonary embolism, and right-to-left Papillary Muscle Rupture
shunting across a patent foramen ovale. A small study suggests
that late-enhancement magnetic resonance imaging has supe- PMR involves the posteromedial papillary muscle (75%) more
rior sensitivity to detect RVI compared with physical exami- often than the anterolateral papillary muscle (25%) because
nation, ECG, and echocardiography [30]. Finally, right heart of the single vascular supply of the former (right coronary or
catheterization demonstrating a right atrial pressure equal or left circumflex artery, depending on dominance). In contrast,
greater than 10 mm Hg or greater than 80% of the pulmonary the anterolateral papillary muscle has a dual vascular supply,
capillary wedge pressure supports the diagnosis of RVI [26]. from the left anterior descending and circumflex arteries. The
Treatment of RVI should emphasize urgent reperfusion, posteromedial papillary muscle consists of one or two trunks
whether by thrombolysis or PCI. Successful reperfusion is as- and multiple heads, all of which extend chordae to both mi-
sociated with significantly improved RV function and clinical tral valve leaflets. Complete or partial rupture of a trunk or
outcome [3133]. Supportive measures are critical as well. In- head leads to varying degrees of mitral regurgitation. (Severe
travenous fluid should be judiciously administered to maintain mitral regurgitation may also occur with leaflet prolapse due to
optimal RV preload. A cautious challenge of 1 to 2 L is a rea- reduced tethering by an infarcted, but nonruptured, papillary
sonable start. Central venous pressure (CVP) monitoring may muscle.)
be helpful in avoiding RV volume overload (CVP exceeding 10 Because PMR may occur despite a limited territory of in-
to 14 mm Hg), which may compromise LV preload via ventric- farction, it is not uncommon for patients to have relatively
ular interdependence [34]. Because right atrial contraction is preserved LV function in comparison to the degree of heart fail-
an important contributor to right-sided output, AV synchrony ure and CS at presentation [39,40]. Patients present with acute
should be maintained, with AV sequential pacing in the case dyspnea due to pulmonary congestion. Physical examination
of complete heart block or conversion to sinus rhythm in the may include a systolic murmur, though this may be absent due
case of atrial fibrillation. In cases where right coronary artery to equalization of left atrial (LA) and LV pressures. Therefore, a
occlusion is proximal to the atrial branches, resulting in right heightened index of suspicion is necessary to distinguish PMR
atrial ischemia, the CVP tracing may demonstrate depressed from pure LV dysfunction.
A-waves and right atrial pacing may fail to capture. Inotropic PMR is suggested by the presence of large V-waves in
support and LV afterload reduction with intra-aortic balloon the pulmonary capillary wedge pressure tracing, although this
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Chapter 40: Mechanical Complications of Myocardial Infarction 423

FIGURE 40.2. A: ECG of patient with inferior STEMI and sinus bradycardia showing ST-segment ele-
vation in lead 3 greater than in lead 2 and ST-segment elevation in lead V1 , suggesting RV involvement.
B: Right-sided placement of precordial leads demonstrates ST-segment elevation in lead V4R , confirming
RVI. In this figure, lead V1 is V1R , V2 is V2R , V3 is V3R , V4 is V4R , V5 is V5R , and V6 is V6R .

finding may also be seen with severe LV dysfunction, VSR, or is reduced with concomitant coronary artery bypass grafting
other causes of mitral regurgitation. The diagnosis of PMR is [41,42]. Long-term survival after surgery ranges from 60% to
made more definitively by echocardiography, on visualization 80%, and is similar to that of matched patients with MI, but
of a flail portion of a mitral valve leaflet or a ruptured papillary no PMR [42].
muscle head prolapsing into the left atrium, along with color
Doppler evidence of mitral regurgitation.
Stabilization may be accomplished with the use of inotropic Ventricular Septal Rupture
agents, afterload reduction if possible, and insertion of an intra-
aortic balloon pump. However, with an in-hospital mortality The presentation of VSR has changed as treatment for acute
of up to 80% and a long-term survival rate of approximately MI has evolved to include fibrinolysis and primary PCI. Be-
6% with medical therapy alone [39,40], urgent surgical re- fore the advent of fibrinolytic and percutaneous reperfusion
pair is indicated. This may consist of chordal-sparing mitral therapies, VSR occurred in 1% to 2% of patients with acute
valve replacement or, if necrosis is limited, papillary muscle MI, with a mean onset of 3 to 5 days after infarction. In the
reimplantation with or without ring annuloplasty. Coronary thrombolytic era, the incidence is approximately 0.2%, with
angiography should be performed so that necessary revascu- a median onset in the first 24 hours after MI [38,43,44]. Ap-
larization may be performed at the time of surgery. Although proximately two thirds of VSR cases occur in the mid- to distal
perioperative mortality (10% to 24%) remains significant, it septum in association with anterior MI; the remainder occur in
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424 Section III: Cardiovascular Problems and Coronary Care

TA B L E 4 0 . 2
CHARACTERISTICS OF MYOCARDIAL RUPTURE

Characteristic Ventricular septal rupture Free wall rupture Papillary muscle rupture

Incidence 1%3% without reperfusion 0.8%6.2%; primary 1%; posteromedial more


therapy; 0.2%0.34% with angioplasty, but not frequent than anterolateral
fibrinolysis; 3.9% in patients fibrinolysis, appears to reduce papillary muscle
with cardiogenic shock risk
Time course Bimodal peak: <24 h and 35 d; Bimodal peak: <24 h and 35 d; Bimodal peak: <24 h and 35 d;
range 114 d range 114 d range 114 d
Clinical manifestations Chest pain, dyspnea, Anginal, pleuritic, or pericardial Abrupt onset of dyspnea due to
hypotension chest pain; syncope, pulmonary edema;
hypotension, arrhythmia, hypotension
nausea, restlessness,
hypotension, sudden death
Physical findings Harsh holosystolic murmur, Jugular venous distention, Soft murmur in some cases, no
thrill, accentuated S2 , S3 , pulsus paradoxus, thrill, variable signs of RV
pulmonary edema, RV and LV electromechanical overload, severe pulmonary
failure, cardiogenic shock dissociation, cardiogenic edema (may be asymmetric),
shock cardiogenic shock
Echocardiographic findings VSR, color Doppler left-to-right Myocardial tear, >5 mm Hypercontractile LV, torn
shunt across septum, RV pericardial effusion not papillary muscle or chordae
dilation, and hypokinesis always visualized; clot within tendineae, flail leaflet, severe
pericardial space, tamponade MR by color Doppler
Cardiac catheterization Oxygen saturation step up from Ventriculography insensitive; No oxygen saturation step up
RA to RV, large V-waves equalization of diastolic from RA to RV (may occur
pressures from RV to PA); large
V-waves, high PCWP

LV, left ventricle; MR, mitral regurgitation; PA, pulmonary artery; PCWP, pulmonary capillary wedge pressure; RA, right atrial; RV, right ventricle;
VSR, ventricular septal rupture.
Adapted from Antman EM, Anbe DT, Armstrong PW, et al: ACC/AHA guidelines for the management of patients with ST-elevation myocardial
infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the
1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Available at www.acc.org/clinical/guidelines/stemi/index.pdf.

the basal septum in association with inferior MI. On the basis The diagnosis of VSR can be made by right heart catheteri-
of the anatomy of the rupture track, VSR may be classified as zation demonstrating a step up in the oxygen saturation (>8%)
simple (directly through and through) or complex (serpiginous, in the RV, to be distinguished from a step up in the pulmonary
with an exit site remote from the entry site); complex VSRs are artery, which is occasionally observed in patients with severe
more frequently noted with inferior MI. Five percent to 10% of mitral regurgitation. In addition, catheterization reveals in-
patients have multiple defects. VSR is typically associated with creased pulmonary-to-systemic flow ratios ( Q p/Q
s >1.4), in-
total occlusion of the infarct-related artery with little or no col- creased right-sided pressures, and large V-waves in the pul-
lateral flow. Risk factors for VSR include advanced age, female monary capillary wedge tracing; left ventriculography may
sex, anterior MI, and no previous smoking [44]. In addition, in identify the rupture site. Echocardiography with color Doppler
patients with anterior MI, the presence of ST-segment elevation imaging is commonly used for both diagnosis and surgical
or Q-waves in the inferior leads, indicating a wrap-around planning. A visible defect may be seen in association with the
left anterior descending artery supplying both the anterior and corresponding anterior or inferior wall motion abnormal-
inferior LV walls, may identify patients at risk for VSR [45]. ity. Continuous wave Doppler interrogation of flow at this
VSR causes sudden shunting of flow from the LV to the pul- site demonstrates dense, high-velocity flow from LV to RV.
monary circulation. This results in impaired forward cardiac Echocardiography also provides information about LV and RV
output. There is acute pressure overload of the RV and volume function and concomitant mitral valve pathology.
overload of the pulmonary circulation and LV, which become Nonsurgical therapy, such as afterload reduction, diuretics,
evident clinically as right heart failure, pulmonary congestion, and inotropic and intra-aortic balloon pump support, is purely
and CS. The degree of shunting depends on the rupture size, temporizing and alone is associated with greater than 90%
the relative resistance of the pulmonary and systemic circula- mortality. Surgical repair of the VSR, first performed in 1957,
tions, and the relative function of the RV and LV. As the LV is definitive. Some have used biventricular mechanical support
fails and systolic pressure decreases, left-to-right shunting de- as a means to restore hemodynamic stability and avoid surgery
creases. If RV pressures exceed those on the left, right-to-left on freshly infarcted tissue, before definitive surgical repair [46].
shunting occurs, resulting in hypoxemia. Surgical repair has improved 30-day mortality from VSR to
Symptoms of VSR include chest pain and dyspnea. In con- 10% to 15% in cases of anterior MI and 30% to 35% in cases
trast to patients with PMR, those with VSR have a harsh pan- of inferior MI. As mortality is higher in patients with com-
systolic murmur at the left sternal border, with a left paraster- plex VSR and in those with RVI [47], the increased mortality
nal thrill in 50%. Signs of RV failure are also present, including with inferior VSRs has been attributed to the more challenging
jugular venous distention and peripheral edema. ECG findings surgical repair due to complex anatomy and basal loca-
include persistent ST-segment elevation and AV nodal or infra- tion and the possibility of concomitant RV infarction. CS
nodal conduction abnormalities. at the time of surgical intervention and incomplete coronary
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Chapter 40: Mechanical Complications of Myocardial Infarction 425

revascularization have also been shown to be strong predictors syncope. Hypotension may be accompanied by inappropri-
of 30-day and long-term mortality [48]. Patients who survive ate bradycardia. New ST-segment elevation or T-wave abnor-
the perioperative period have been reported to have a long-term malities may be evident. Pseudoaneurysms can be diagnosed by
survival rate of approximately 60% to 80%. echocardiography, contrast or radionuclide ventriculography,
Recently, percutaneous transcatheter closure of VSR has or magnetic resonance imaging. Diagnostic pericardiocentesis
been reported in a limited number of patients; appropriate may yield blood; therapeutic pericardiocentesis may destabi-
patient selection, technical aspects of device selection and lize a contained effusion and result in death. Surgical repair
placement, durability of occlusion, and long-term outcome are is usually necessary, although survival with pericardiocentesis
unknown. and supportive medical therapy has been reported in selected
patients [50].

Free Wall Rupture


LV free wall rupture is by far the most common of all ruptures
LEFT VENTRICULAR
and usually results in sudden death. The temporal pattern of REMODELING:
rupture has two peaks, the first within 24 hours and the second
between 3 and 5 days after acute MI [49]. Risk factors for free
PATHOPHYSIOLOGY, CONTEXT,
wall rupture are similar to those for VSR, whereas successful PREVENTION, AND NATURAL
early reperfusion and presence of collateral flow are important HISTORY
preventive factors. Pericardial tamponade and electromechan-
ical dissociation often develop quickly, in which case death is Injuries to the LV that decrease systolic performance, such as
inevitable without treatment. acute MI, trigger a sequence of histopathologic events that lead
LV pseudoaneurysm develops if free wall rupture is con- to changes in LV size, shape, and function. This process of
tained by adherent pericardium or clot formation, thus prevent- remodeling is initially compensatory but becomes maladap-
ing immediate pericardial tamponade and death. Symptoms tive, with progressive hypertrophy, dilation, spherical distor-
of contained rupture include recurrent chest pain or pleurisy, tion, and impairment of contractile function, and is associ-
emesis without preceding nausea, unexplained restlessness, and ated with heart failure progression and poor clinical outcome.

FIGURE 40.3. Ventricular remodeling after MI. AII, angiotensin II; ACE, angiotensin-converting enzyme;
ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; CO, cardiac output; ECM, extracellular
matrix; ET, endothelin; MMP, matrix metalloproteinase; NE, norepinephrine; RAAS, reninangiotensin
aldosterone system; TGF, transforming growth factor; TIMP, tissue inhibitor of metalloproteinase. [From
Sutton MG, Sharpe N: Left ventricular remodeling after myocardial infarction: pathophysiology and
therapy. Circulation 101:29812988, 2000, with permission.]
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426 Section III: Cardiovascular Problems and Coronary Care

Because LV remodeling is concordant with clinical outcomes TA B L E 4 0 . 3


over the natural history of heart failure, its prevention has been
accepted as a reasonable therapeutic target. SUMMARY OF RECOMMENDATIONS BASED ON
The early phase of remodeling begins within 3 hours of MI RANDOMIZED CONTROLLED CLINICAL TRIALS
and consists of infarct expansion due to collagen degradation
by serine proteases and matrix metalloproteinases [51]. The Cardiogenic shock: Early revascularization by PCI or
resultant wall thinning and ventricular dilatation increase ven- CABG in patients younger than 75 years who are otherwise
tricular wall stress, thus promoting later remodeling, which in- suitable candidates reduces 1-year mortality. Patients older
cludes collagen scar formation, fibrosis, and myocyte hypertro- than 75 years may also benefit from early revascularization
phy. The abnormal stresses related to mitral regurgitation [52] and an individualized treatment strategy is recommended
or ventricular mechanical dyssynchrony [53] resulting from the [18]
MI, if present, further promote remodeling. Remodeling: ACE inhibition or angiotensin-receptor
The reninangiotensinaldosterone (RAAS) and sympa- blockade in patients with evidence of LV dysfunction after
thetic nervous systems are central mediators of remodeling MI attenuates LV remodeling and improves survival
[51,54] (Fig. 40.3). Myocyte stretch from increased wall stress [5558]
stimulates the local production of angiotensin II, which in turn Remodeling: Beta-blockade in patients with evidence of LV
promotes myocyte hypertrophy, fibroblast proliferation, and dysfunction after MI attenuates LV remodeling and
collagen production. Adrenergic stimulation, in response to improves survival and LV remodeling [60,61]
myocardial injury and/or hemodynamic compromise, leads to
ACE, angiotensin-converting enzyme; CABG, coronary artery bypass
myocardial production of cytokines, such as TNF-, IL-1, graft; LV, left ventricle; MI, myocardial infarction; PCI, percutaneous
and IL-6, which mediate myocyte hypertrophy, apoptosis, and coronary intervention.
changes in the extracellular matrix. Furthermore, adrenergic
stimulation enhances the activity of the RAAS. Finally, there
is growing evidence that oxidative stress after MI plays a role
in the apoptosis, inflammation, fibrosis, and hypertrophy pro- blockade in patients without contraindication has also been
cesses of myocardial remodeling. shown to improve survival in patients with LV dysfunction
Therapies to prevent or reduce postinfarction remodeling after MI [59].
have focused on limiting infarct expansion and moderating the There are several potential mechanisms of benefit from beta-
neurohormonal axes. Infarct expansion and remodeling are in- blockade. Beta-blockers reduce myocyte apoptosis, collagen
fluenced by the size and location of the original infarct, pa- deposition, and hypertrophy; they reduce myocardial oxygen
tency of the infarct-related artery, presence of collateral flow, demand by reducing heart rate and blood pressure, which may
regional wall thickness, and radius of curvature. Reperfusion be especially beneficial for hibernating myocardium; and they
of the infarct-related artery restores stunned myocardium in directly oppose catecholamine stimulation of myocytes. Spe-
the infarct border zone, reduces infarct size, and improves ven- cific agents may have additional effects, such as the antioxi-
tricular function and long-term prognosis. dant and anti-inflammatory properties of carvedilol. Evidence
Blockade of the RAAS and sympathetic nervous system is of the benefit of beta-blockade includes early studies showing
the cornerstone of pharmacologic therapy directed at inter- reduced remodeling in patients not receiving ACE inhibitors.
rupting remodeling and improving long-term outcome. The The Carvedilol Post-Infarct Survival Control in LV Dysfunction
mechanisms of action of angiotensin-converting enzyme (ACE) (CAPRICORN) study demonstrated that beta-blockade with
inhibitors include beneficial effects on hemodynamics and load- carvedilol after MI improved all-cause mortality and ventricu-
ing conditions, as well as direct effects on remodeling. ACE lar remodeling in patients already receiving standard ACE in-
inhibition attenuates the increase in LV volume occurring after hibitor treatment [60,61]. The survival benefit of beta-blockers
MI and earlier commencement of ACE inhibition appears to is greatest in patients at highest risk for adverse events, such
produce greater benefit. This translates into a survival benefit as those with LV dysfunction, ventricular arrhythmias, and no
in all patients with MI, including those with evidence of LV reperfusion.
dysfunction, as demonstrated in the Survival and Ventricular Finally, patients with MI should be followed to determine
Enlargement (SAVE) and Acute Infarction Ramipril Efficacy whether they would benefit from cardiac resynchronization
(AIRE) studies [5557]. It is recommended that all patients therapy for mechanical dyssynchrony [62] or intervention for
without contraindications such as hyperkalemia or azotemia mitral regurgitation [63].
be treated with ACE inhibitors after STEMI. Patients who are Recommendations for the management of the mechanical
intolerant of ACE inhibitors appear to derive similar benefit complications of MI on the basis of randomized controlled
from angiotensin receptor blockers (ARB) [58]. Aldosterone trials are summarized in Table 40.3.

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28. Robalino BD, Whitlow PL, Underwood DA, et al: Electrocardiographic man- and morbidity in patients with left ventricular dysfunction after myocar-
ifestations of right ventricular infarction. Am Heart J 118:138144, 1989. dial infarction. Results of the survival and ventricular enlargement trial. The
29. Braat SH, Brugada P, de Zwaan C, et al: Value of electrocardiogram in diag- SAVE Investigators. N Engl J Med 327:669677, 1992.
nosing right ventricular involvement in patients with an acute inferior wall 57. Effect of ramipril on mortality and morbidity of survivors of acute my-
myocardial infarction. Br Heart J 49:368372, 1983. ocardial infarction with clinical evidence of heart failure. The Acute In-
30. Kumar A, Abdel-Aty H, Kriedemann I, et al: Contrast-enhanced cardiovas- farction Ramipril Efficacy (AIRE) Study Investigators. Lancet 342:821828,
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Cardiol 48(10):19691976, 2006. 58. Pfeffer MA, McMurray JJ, Velazquez EJ, et al: Valsartan, captopril, or both
31. Bowers TR, ONeill WW, Grines C, et al: Effect of reperfusion on biventric- in myocardial infarction complicated by heart failure, left ventricular dys-
ular function and survival after right ventricular infarction. N Engl J Med function, or both. N Engl J Med 349:18931906, 2003.
338:933940, 1998. 59. Pitt B, Remme W, Zannad F, et al: Eplerenone, a selective aldosterone blocker,
32. Kinn JW, Ajluni SC, Samyn JG, et al: Rapid hemodynamic improvement after in patients with left ventricular dysfunction after myocardial infarction. N
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1234, 1995. 60. Dargie HJ: Effect of carvedilol on outcome after myocardial infarction in pa-
33. Pfisterer M: Right ventricular involvement in myocardial infarction and car- tients with left-ventricular dysfunction: the CAPRICORN randomised trial.
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34. Berisha S, Kastrati A, Goda A, et al: Optimal value of filling pressure in 61. Doughty RN, Whalley GA, Walsh HA, et al: Effects of carvedilol on left
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435, 2007. 52(5):319326, 2008.
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428 Section III: Cardiovascular Problems and Coronary Care

CHAPTER 41 VENTRICULAR TACHYCARDIA


MELANIE MAYTIN AND BRUCE A. KOPLAN

INTRODUCTION WIDE QRS MONOMORPHIC


Ventricular tachycardia (VT) is defined as a wide QRS com-
TACHYCARDIA
plex tachycardia (QRS width 0.12 second) of three or more Monomorphic tachycardias have the same QRS configuration
consecutive beats at a rate faster than 100 per minute. VT from beat to beat (Figs. 41.1A and 41.2). The differential di-
arises from either reentry or automaticity in the ventricu- agnosis of this type of wide QRS complex tachycardia includes
lar myocardium or Purkinje system below the level of the VT, supraventricular tachycardia (SVT) with aberrant inter-
His bundle. One of the common ways in which VT is clas- ventricular conduction (bundle branch block; Fig. 41.3), and
sified is whether it is sustained or not. Nonsustained VT pre-excited SVT due to antegrade conduction from atrium to
(NSVT) is that which terminates spontaneously within 30 sec- ventricle through an accessory pathway (Fig. 41.4B), or pre-
onds without causing severe symptoms. Spontaneous sustained excited QRS complexes during atrial fibrillation (AF) or atrial
VT requires an intervention, such as cardioversion or antiar- flutter (Fig. 41.3C). The differentiation is critical for prognosis
rhythmic drug (AAD) administration for termination, or pro- and long-term management.
duces severe symptoms, such as syncope, prior to termination.
VTs lasting longer than 30 seconds are usually designated as
sustained.
Another way to classify VT is based on the QRS morphology Initial Evaluation
(Fig. 41.1). Morphologic classifications include monomorphic
VT (the same morphology from beat to beat), polymorphic Hemodynamic instability is an indication for electrical car-
VT (PMVT, varying morphologies from beat to beat), and si- dioversion. If the patient is hemodynamically stable, a limited
nusoidal VT (when the QRS has a duration similar to that of history and physical examination should be performed and a
diastole). Torsades de pointes (TDP) is a unique subcategory 12-lead ECG obtained. The presence of hemodynamic stabil-
of PMVT associated with QT prolongation. ity does not indicate that the tachycardia is supraventricular.
VT can also be classified on the basis of its hemodynamic Hemodynamic stability is dependent on the rate of the tachy-
effects that are largely dependent on the rate of the tachycar- cardia, underlying ventricular function, and the sympathetic
dia and the presence of underlying myocardial dysfunction. nervous system response to tachycardia. VT can be hemody-
Indeed, for all sustained wide QRS tachycardias the first pri- namically stable, SVT may cause hemodynamic collapse, and
ority is to determine whether the patient is hemodynamically vice versa. Wide QRS tachycardias should be managed as VT
stable, with adequate blood pressure and perfusion. Pulseless unless the diagnosis of SVT can be confirmed. Patients with a
VT is associated with no significant cardiac output and is ap- history of structural heart disease are more likely to have VT,
proached in a similar manner as ventricular fibrillation (VF). whereas the absence of structural heart disease favors the diag-
VT can also be hemodynamically stable. This hemodynamic nosis of SVT. Wide QRS tachycardia in patients with a history
classification may be the most relevant classification system of myocardial infarction can be assumed to VT with greater
for initial management. Continuous electrocardiograph (ECG) than 95% certainty [1].
monitoring should be implemented and a defibrillator should The physical examination is occasionally helpful in detect-
be at the patients bedside for immediate use, even if the patient ing the presence of dissociation between atrium and ventricle
is hemodynamically stable. If the patient is pulseless and has (AV dissociation) confirming VT as the diagnosis. Cannon a-
impaired consciousness, angina, or severe pulmonary edema, waves in the jugular venous pulse occurring intermittently and
prompt electrical cardioversion is warranted. Further therapy irregularly during VT indicate periodic contraction of the right
after cardioversion is determined by the type of tachycardia atrium against a closed tricuspid valve. AV dissociation may
and underlying heart disease. also cause variability in the intensity of the first heart sound
If the patient is hemodynamically stable, a brief history and and beat-to-beat variability in systolic blood pressure due to
a 12-lead ECG should be immediately obtained. The immedi- the variable contribution of atrial contraction to left ventricu-
ate history should include determination of known heart dis- lar filling. The absence of evidence of AV dissociation does not
ease, in particular prior myocardial infarction, present medi- exclude the diagnosis of VT. Some patients have conduction
cations, history of prior arrhythmias, whether the patient has from ventricle retrogradely over the His-Purkinje system and
an implanted defibrillator or pacemaker, and drug allergies. AV node to the atrium (VA conduction) during VT. Each ven-
A limited initial physical examination should include the car- tricular beat is accompanied by a cannon a-wave, a finding
diovascular system and lungs. A 12-lead ECG should also be that is also seen in some SVTs (Table 41.1).
obtained following conversion of the tachycardia to compare
the tachycardia QRS to that during sinus rhythm, as well as to
evaluate underlying events, such as myocardial infarction, and Electrocardiogram
QT interval prolongation, or other changes suggestive of elec-
trolyte abnormalities. Previous ECGs are also helpful in this VT can be somewhat irregular at its initiation, but persistence
regard. of an irregularly irregular wide QRS suggests AF with bundle
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Chapter 41: Ventricular Tachycardia 429

C
FIGURE 41.1. Three different wide QRS tachycardias are shown. A: monomorphic VT; B: polymorphic
VT; and C: sinusoidal VT due to hyperkalemia. VT, ventricular tachycardia.

branch block or conduction over an accessory pathway rather 1. AV dissociation: Dissociation of P-waves (if identifiable) and
than VT (Fig. 41.4). Comparing the QRS complex morphol- QRS complexes suggests VT (Fig. 41.2). Because they may
ogy during tachycardia with that of sinus rhythm on an old be partially buried in the QRS complex, or T-wave, the P-
ECG or following cardioversion can be helpful. An identical waves may be difficult to identify. Comparison of the con-
QRS morphology during tachycardia and sinus rhythm sug- tour of QRS and T-waves from beat to beat may be helpful;
gests SVT [2] (with the uncommon exception of bundle branch P-waves may be evident as a slight deflection occurring at
reentry described later in the chapter). An old ECG may also regular intervals independent of QRS complexes. AV disso-
reveal a short PR interval with -waves (Fig. 41.3A) that sug- ciation is probably the most reliable clue to the diagnosis of
gests WolffParkinsonWhite (WPW) syndrome with an acces- VT, especially if a nonsustained run of wide WCT is caught
sory pathwaymediated wide complex tachycardia (WCT; Fig. only on a telemetry rhythm strip.
41.3B). When the onset of tachycardia is recorded, initiation AV dissociation is also indicated by QRS fusion or cap-
by a premature P-wave suggests SVT. ture beats. Fusion beats occur when a supraventricular im-
The following ECG criteria applied in a stepwise approach pulse conducts over the AV node and depolarizes a por-
provide reasonable sensitivity and specificity to differentiate tion of the ventricle simultaneously with excitation from the
SVT from VT (Figs. 41.5 and 41.6) [3]. tachycardia focus. They occur if AV dissociation is present

FIGURE 41.2. Sustained monomorphic ventricular tachycardia is present. Dissociated P-waves can be
seen (arrows) with occasional fusion beats (stars) that occur when a sinus P-wave occurs with timing
appropriate to conduct to the ventricle.
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430 Section III: Cardiovascular Problems and Coronary Care

Sinus rhythm FIGURE 41.3. Features of the


WolffParkinsonWhite syndrome
Antidromic AV reentry LA AP leading to pre-excited tachycardias
are shown. A: sinus rhythm is
RA shown. The ECG shows a short PR
interval and -wave. The mechanism
LV is shown in the schematic. Conduc-
LA AP RV tion of the sinus impulse (arrows)
RA propagates over the AV node to the
ventricles and over the accessory
B pathway (AP) to the ventricles.
RV LV Conduction through the accessory
pathway is faster than the AV node,
producing the -wave. B: antidromic
AV reentry is present. Tachycardia
A is due to circulation of the reentry
wave front from atrium to ventricle
over the accessory pathway, through
the ventricle, and retrograde up the
Atrial fibrillation
AV node to the atrium. Pre-excited
AP antidromic tachycardia is often
indistinguishable from ventricular
tachycardia. C: atrial fibrillation with
rapid conduction over an accessory
LV pathway is shown. Tachycardia is
RV irregular, although at the very rapid
C
rate, the irregularity can be difficult
to appreciate.

B
FIGURE 41.4. A: A wide QRS tachycardia with a left bundle branch block configuration. B: Following
administration of drugs to slow down atrioventricular (AV) conduction atrial flutter is present with a
narrow QRS configuration. Thus, A shows atrial flutter with aberrant conduction.
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Chapter 41: Ventricular Tachycardia 431

TA B L E 4 1 . 1
SUPRAVENTRICULAR TACHYCARDIA VERSUS LBB Configurations RBB Configurations
VENTRICULAR TACHYCARDIA Favoring VT Favoring VT

R > 30 ms Monophasic R
Findings suggesting ventricular tachycardia
AV dissociation
V1
R - S > 60 ms
Electrocardiogram or QR

Dissociated P-waves V2
Notched S RS
Fusion beats, capture beatsindicate conduction of a
fortuitously timed P-wave from atrium to ventricle
before the ventricle is completely depolarized from the R/S < 1
VT focus or circuit V6 QR
AV dissociation on physical examination QS
QR
QS
Intermittent cannon a-waves in jugular venous pulse
Beat-to-beat variability in S1 and systolic blood pressure
ECG leads V1 V6
QRS concordance: The absence of an rS or Rs complex in FIGURE 41.6. Electrocardiogram findings indicative of ventricular
any precordial lead tachycardia (VT) or supraventricular tachycardia with aberrant con-
duction are shown. LBB, left bundle branch; RBB, right bundle
RS >100 ms: An interval between the onset of the R and the
branch.
nadir of the S-wave >100 ms in any precordial lead
Left bundle branch block VT
Initial R-wave in lead V1 >30 ms in duration
Interval from onset of R to nadir of S in V1 >60 ms If the diagnosis cannot be made after assessment for these
Notching in the downstroke of the S-wave in lead V1 features, a more thorough evaluation of the QRS morphol-
In V6 , a QS or QR pattern ogy on the 12-lead ECG can be helpful (Fig. 41.6) [3]. For
Right bundle branch block VT left bundle branch block morphology tachycardias, an initial
V1 : A monophasic R, QR, or RS pattern R-wave in lead V1 of greater than 30 ms in duration or a du-
V6 : An R to S <1 or a QS or a QR pattern ration of greater than 60 ms from the onset of the R-wave to
the nadir of the S-wave in V1 suggests VT. Notching in the
downstroke of the S-wave in lead V1 also suggests VT. In V6 , a
QS or QR pattern suggests VT. For right bundle branch block
and the VT is not particularly fast. Fusion beats have a QRS (RBBB) morphology tachycardias, a monophasic R, QR, or RS
morphology that is typically intermediate between that of a pattern in V1 suggests VT. In V6 , an R-to-S amplitude ratio of
supraventricular beat and a ventricular beat. Capture beats less than 1 or QS or QR patterns suggests VT.
have a similar significance to fusion beats. They occur when
a supraventricular beat is able to conduct to the ventricles,
depolarizing the ventricle in advance of the next tachycardia Electrocardiographic Artifacts that Mimic Wide
beat. These beats are morphologically identical to the QRS Complex Tachycardia
complex seen in sinus rhythm but occur in the midst of a
wide QRS complex tachycardia. Misinterpreting an electrocardiographic artifact, such as the
2. QRS concordance: The absence of an rS or Rs complex in one shown in Figure 41.7, as VT is a common error that has
any precordial lead (V1 to V6 ) suggests VT. led to inappropriate and invasive procedures including cardiac
3. RS >100 ms: An interval between the onset of the R and the catheterization, implantation of defibrillators, and even the oc-
nadir of the S-wave greater than 100 ms in any precordial casional precordial thump [4]. Normal QRS complexes are
lead (V1 to V6 ) favors VT. often visible marching through the artifact at the sinus rate
(arrows in Fig. 41.7). One author has referred to this as the
notches sign because only small notches may be seen that
march through the artifact at intervals that are the same as the
VT versus SVT RR intervals preceding the onset of tachycardia [5]. The his-
tory of the patients activity at the time of the recording is often
helpful in suggesting artifact. The recording in Figure 41.7 was
AV dissociation VT
Yes performed during toothbrushing. Artifacts are also commonly
No caused by tremors, shivering, and electrical noise. The absence
of symptoms or hemodynamic instability during the event (es-
rS or Rs in V1 to V6 VT
No pecially if the recording suggested a very fast heart rate) also
Yes suggests artifact.
r-S > 100 ms in any of V1 to V6 VT
Yes
No
ACUTE TREATMENT OF WIDE
Indeterminate
COMPLEX TACHYCARDIA
Proceed to morphology criteria for RBBB or LBBB QRS
The misdiagnosis of VT as SVT followed by delivery of an
FIGURE 41.5. The schematic for an algorithm for ECG diagnosis inappropriate therapy is common in patients with wide QRS
of VT is shown. LBBB, left bundle branch block; RBBB, right bun- tachycardias [6]. As a general rule, wide QRS tachycardia
dle branch block; SVT, supraventricular tachycardia, VT, ventricular should be treated as VT unless the diagnosis of SVT can be
tachycardia. confirmed.
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432 Section III: Cardiovascular Problems and Coronary Care

FIGURE 41.7. Apparent nonsustained ventricular tachycardia is actually artifact. Arrows indicate the
sinus rhythm QRS complexes that march through the artifact.

persists after defibrillation, CPR should be promptly resumed


MANAGEMENT OF and five cycles completed prior to additional therapy. When
HEMODYNAMICALLY VT/VF is revealed during a rhythm check, CPR should be pro-
vided while the defibrillator is charging and resumed immedi-
UNSTABLE VT/VF ately following shock delivery. The algorithm for VF/pulseless
VT should be followed (Fig. 41.8). Either epinephrine or va-
Figure 41.8 provides an algorithm for the management of
sopressin can be used as a first-line vasopressor agent if CPR
hemodynamically unstable VT or VF. Hemodynamically unsta-
continues to be required after two unsuccessful attempts at
ble wide QRS tachycardia that is not due to sinus tachycardia
cardioversion [7]. If vasopressin is used, a one-time dose is ap-
with bundle branch block or artifact requires immediate elec-
propriate as it has a half-life of 20 to 30 minutes. Epinephrine
trical cardioversion. Both good basic life support (BLS) with
can be administered in 1-mg doses every 3 to 5 minutes.
prompt and efficient cardiopulmonary resuscitation (CPR) and
Although definitive evidence of a long-term mortality ben-
rapid defibrillation are the most important measures to im-
efit of any AADs for acute management of VT/VF is lacking,
prove survival in unstable VT/VF [7]. Survival from VT/VF ar-
these agents should be used when initial attempts of electrical
rest diminishes by 7% to 10% per minute between collapse and
cardioversion are not successful [11,12]. When VF/pulseless
defibrillation if CPR is not performed [8]. In fact, several stud-
VT persists after three shocks plus CPR and administration of
ies have shown that survival from VT/VF arrest can be doubled
a vasopressor, consider administering an antiarrhythmic, such
or tripled if CPR is provided [9,10]. In keeping with these data,
as amiodarone. If amiodarone is unavailable, lidocaine may be
the most recent American Heart Association guidelines for car-
considered. Magnesium should also be considered for TDP as-
diopulmonary resuscitation emphasize an integrated strategy
sociated with a long QT interval [7]. In a trial of 504 patients
of combined CPR and defibrillation [7]. If pulseless VT/VF

Hemodynamically Unstable Wide QRS Tachycardia or Ventricular Fibrillation

Shock (x1)
120-200J biphasic (device dependent)
If unknown, use 200J

Resume CPR immediately


Complete 5 cycles of
CPR & recheck rhythm
VT/VF

Evaluate and Treat Potential Etiologies: Shock (x1)


Long QT
Magnesium
Pacing Resume CPR immediately
Isoproterenol Epinephrine or Vasopressin
Ischemia Complete 5 cycles of
Complete 5 cycles of
Anti-ischemic therapy CPR & recheck rhythm CPR & recheck rhythm
Hyperkalemia
VT/VF
Calcium
Bicarbonate
Albuterol Shock (x1)
Resins
Dialysis
Drug toxicity
Bicarbonate Resume CPR immediately
Beta-blockers Amiodarone or Lidocaine
Digoxin Fab Consider magnesium

FIGURE 41.8. The algorithm for management of hemodynamically unstable ventricular tachycardia (VT)
or ventricular fibrillation (VF) is shown.
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Chapter 41: Ventricular Tachycardia 433

with out-of-hospital VF or pulseless VT who failed three at- chapter). If the initial agent selected is ineffective, cardioversion
tempted cardioversions, administration of 300 mg of intra- is usually warranted.
venous (IV) amiodarone was more effective than placebo for First-line antiarrhythmic agents for stable wide QRS tachy-
restoration of circulation and survival to hospital admission cardia of uncertain origin include procainamide, amiodarone,
(44% of treated patients vs. 34% of untreated patients). Sur- and in some circumstances, lidocaine. It is also appropriate
vival to hospital discharge was not improved and more patients to use electrical cardioversion as the initial therapy for sta-
who received amiodarone had hypotension (59% vs. 48%) or ble tachycardia if appropriate sedation is available and can be
bradycardia (41% vs. 25%) [7,13,14]. Administration of IV safely achieved. Current ACLS guidelines state that IV admin-
procainamide can be considered as an alternative agent, but istration of amiodarone, procainamide, sotalol (not available
the data supporting its efficacy are limited [15]. Administra- in IV form in the United States), and beta-blockers are prefer-
tion of IV lidocaine is most appropriate in the management of able to lidocaine. Lidocaine is usually ineffective for treatment
unstable VT/VF during suspected acute myocardial ischemia of sustained VT that is not due to acute myocardial ischemia
or infarct [1618]. or infarction [7,19]; procainamide and sotalol both have been
Although bretylium is an acceptable alternate antiarrhyth- shown to be more efficacious in this setting [20,21]. Pro-
mic agent for VT, it has been removed from advanced cardiac cainamide and sotalol have negative inotropic effects and can
life support (ACLS) guidelines due to a combination of global induce hypotension. These agents should be avoided in patients
supply shortage and lack of evidence showing its superiority with significantly impaired ventricular function (left ventricular
over any of the previously mentioned AADs. Bretylium has ejection fraction <0.40) in favor of IV amiodarone [18,22,23].
similar efficacy to amiodarone for treatment of hemodynami- Procainamide is acetylated to n-acetylprocainamide (NAPA).
cally destabilizing VT that has failed cardioversion, but is as- NAPA is a class III AAD that can cause TDP and is excreted
sociated with a greater incidence of hypotension compared to entirely by the kidney; therefore, procainamide should also be
IV administration of amiodarone [7,18]. avoided in patients with significant renal dysfunction. Each
of these treatments (procainamide, amiodarone, or cardiover-
sion) is also appropriate for SVT with aberrant conduction
and therefore for wide QRS tachycardias of uncertain origin.
MANAGEMENT OF If an accessory atrioventricular pathway with rapid repetitive
HEMODYNAMICALLY STABLE conduction during AF or flutter is suspected (Fig. 41.3C), ad-
ministration of IV procainamide or cardioversion are first-line
WIDE QRS TACHYCARDIA therapies.
In the absence of signs or symptoms of impaired consciousness
or tissue hypoperfusion, a 12-lead ECG should be obtained to
attempt to differentiate VT from SVT [7]. In patients in whom POLYMORPHIC VENTRICULAR
the diagnosis of SVT with aberrancy is suspected, the response TACHYCARDIA
to vagal maneuvers or adenosine administration while record-
ing the ECG may also elucidate the diagnosis (Fig. 41.4). Vago- VT with a continually changing QRS morphology is referred to
tonic maneuvers and administration of IV adenosine often ter- as PMVT and is most often due to cardiac ischemia, metabolic
minate or expose SVT and usually have no effect on VT. Close disarray, or drug toxicity, often associated with QT prolonga-
monitoring is required during these maneuvers; hypotension or tion. PMVT is often self-terminating, but likely to recur with
precipitation of VF can rarely occur. a significant risk of hemodynamic instability and degeneration
If the diagnosis remains unknown, the choice of initial an- to VF.
tiarrhythmic agent should be influenced by the hemodynamic The combination of PMVT and QT interval prolongation
stability and rhythm analysis (Fig. 41.9). Administration of (usually a corrected QT interval [QTc]) greater than 500 ms
multiple antiarrhythmic agents should be avoided as polyphar- is called torsades de pointes. The name is derived from the
macy increases the risk of precipitating incessant, although electrocardiographic appearance of twisting around the base-
usually slower VT or new VTs, such as TDP (see later in the line as displayed in Figure 41.10. QT prolongation can be

Stable Wide QRS Tachycardia

Irregular
Regular tachycardia
tachycardia

VT or uncertain SVT with AF with Pre-excited AF


rhythm aberrancy aberrancy

Amiodarone Attempt vagal Beta-blockers Procainamide,


maneuvers or or diltiazem ibutilide, amiodarone,
Prepare for elective
adenosine or synchronized
synchronized
cardioversion
cardioversion

FIGURE 41.9. The algorithm for management of hemodynamically tolerated wide QRS tachycardia is
shown. AF, atrial fibrillation; SVT, supraventricular tachycardia, VT, ventricular tachycardia.
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434 Section III: Cardiovascular Problems and Coronary Care

B
FIGURE 41.10. Two episodes of polymorphic ventricular tachycardia (VT) are shown. A: Polymorphic
VT is due to acute myocardial infarction. The QT interval is normal prior to the onset of tachycardia.
B: Torsades de pointes associated with QT prolongation prior to the onset of the tachycardia is present.
A pause precedes onset of tachycardia.

acquired due to electrolyte abnormalities, QT-prolonging TA B L E 4 1 . 2


drugs, bradycardia, or a congenital ion channel disorder. A
list of the acquired etiologies of TDP is provided in Table 41.2; CAUSES OF TORSADES DE POINTES OR QT
a more extensive list is available at the QTdrugs.org Web site PROLONGATION
maintained and updated by the University of Georgetown, De-
partment of Pharmacology. TDP often has a characteristic on- Congenital long QT syndrome
set (Fig. 41.10B). A slowing of heart rate or pause produced Bradycardia Risperidone
by a premature ventricular contraction (PVC) further prolongs Electrolyte abnormalities Sertraline
the QT interval. The T-wave of the longer QT interval is in- Hypokalemia Thioridazine
terrupted by the first beat of the PMVT. Thus, TDP is often Hypomagnesemia Venlafaxine
referred to as pause dependent. Hypocalcemia Ziprasidone
TDP that leads to VF should immediately be defibrillated. Central nervous system disorders Antibiotics
Recurrent TDP is frequently suppressed by IV magnesium sul- Subarachnoid hemorrhage Clarithromycin
fate (1 to 2 g) that can be repeated in 5 to 15 minutes if no ini- Drugs Erythromycin
tial effect is seen [24]. Magnesium administration suppresses Antiarrhythmics Foscarnet
ventricular ectopy, but does not shorten the QT interval. It Amiodarone Gatifloxacin
is often effective even if serum magnesium concentration is Disopyramide Halofantrine
in the normal range. If ventricular ectopy recurs after initial Dofetilide Levofloxacin
administration, additional doses are warranted. Administra- Dronedarone Moxifloxacin
tion of large, repeated doses of magnesium should be avoided Ibutilide Pentamidine
in the presence of severe renal insufficiency; hypermagnesemia Quinidine Miscellaneous drugs
with neuromuscular depression and respiratory arrest can oc- Procainamide Arsenic trioxide
cur. Neuromuscular depression is reversed by administration Sotalol Bepridil
of IV calcium. Antipsychotics, antidepressants, Indapamide
Correction of other electrolyte abnormalities and discontin- hypnotics, and anticonvulsants Isradipine
uation of all medications that can prolong the QT interval is Chlorpromazine Levomethadyl
warranted. Because bradycardia prolongs the QT interval and Desipramine Moexipril/HCTZ
increases the risk for further TDP, increasing heart rate with Doxepin Naratriptan
pacing, atropine, or isoproterenol administration can also sup- Droperidol Nicardipine
press recurrent episodes of TDP. Temporary ventricular pacing Felbamate Octreotide
is most reliable and should be implemented at a heart rate of Fluoxetine Probucol
110 to 120 beats per minute and then titrated lower guided Fosphenytoin Salmeterol
by suppression of ventricular ectopy. Because of its effect on Haloperidol Sparfloxacin
increasing oxygen demand, isoproterenol is contraindicated if Imipramine Sumatriptan
active cardiac ischemia is suspected. Mesoridazine Tacrolimus
PMVTs other than TDP are most commonly associated Paroxetine Tamoxifen
with acute myocardial ischemia and should be managed with Pimozide Tizanidine
anti-ischemic strategies including beta-blockers and revascu- Quetiapine Zolmitriptan
larization. IV lidocaine and amiodarone can be considered for
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Chapter 41: Ventricular Tachycardia 435

recurrent episodes. If the cause of PMVT is unclear, such that syndrome (Fig. 41.3). These pre-excited tachycardias can be
both TDP and ischemia are possibilities, administration of due to antidromic AV reentry (Fig. 41.3B) or AF or flutter con-
IV magnesium and lidocaine are reasonable initial therapies, ducting from atrium to ventricle over the accessory pathway
which are unlikely to aggravate arrhythmias from either cause. (Fig. 41.3C). Clues that a wide QRS tachycardia may be a pre-
excited tachycardia include: evidence of WPW on a prior ECG,
with a short PR interval and a -wave (Fig. 41.3A); AF with a
SINUSOIDAL VENTRICULAR very fast ventricular response of 200 to 300 beats per minute
(Fig. 41.3C); and irregularly irregular WCT with variation in
TACHYCARDIA beat-to-beat QRS morphology. Each QRS complex represents
When the QRS has a similar duration to that of diastole, the some degree of fusion between conduction over the accessory
tachycardia has a sinusoidal appearance (Fig. 41.1C). This is pathway and conduction through the AV node.
due to either very rapid monomorphic VT, also called ventric- Pre-excited tachycardias should generally be managed as
ular flutter, which can occur due to any of the causes given VT. Procainamide, which slows accessory pathway conduc-
previously in the chapter, or acute myocardial ischemia. Slow tion, or electrical cardioversion are first-line therapies. IV li-
sinusoidal VT (Fig. 41.1C) occurs when the QRS is prolonged docaine usually has little effect. Administration of medications
as a consequence of slowing of conduction through the my- that suppress AV nodal conduction without suppressing con-
ocardium. Such slow ventricular conduction is most commonly duction over the accessory pathway can accelerate the ventricu-
due to hyperkalemia or toxicity from a drug that blocks car- lar response, precipitating VF or hemodynamic collapse. Thus,
diac sodium channels, such as flecainide, propafenone, quini- beta-blockers, diltiazem, verapamil, digoxin, and adenosine are
dine, procainamide, disopyramide, phenothiazines, or tricyclic contraindicated in this setting. IV amiodarone may also have
antidepressants. this effect, because it suppresses AV conduction and should be
Hyperkalemia should be treated with administration of 1 g administered with caution [28].
of IV calcium chloride or calcium gluconate, which promptly
antagonizes the electrophysiologic effects of hyperkalemia. Ad-
ministration of sodium bicarbonate intravenously also has
almost-immediate effects. Calcium and NaHCO3 should not
IMPLANTABLE CARDIOVERTER
be administered together in the same IV line, as they precipi- DEFIBRILLATORS
tate. Administration of hypertonic glucose and insulin has an
effect in several minutes. The duration of action of these mea- Implantable cardioverter defibrillators (ICDs) are a first-line
sures is transient, but does allow institution of measures to re- therapy for many patients who have been resuscitated from a
move potassium with forced diuresis, potassium-binding resins prior cardiac arrest or who are at high risk for arrhythmias and
(Kayexalate), or hemodialysis. sudden cardiac death. An increasing number of patients with
Slow sinusoidal VT due to toxicity from a sodium channel defibrillators are encountered in intensive care units (ICUs).
blocking drug may respond to administration of hypertonic Even when an ICD is present and programmed on, its pres-
sodium in the form of sodium bicarbonate or sodium lactate ence should not delay implementation of standard ACLS when
[25,26]. Sodium bicarbonate administration is indicated for VT or VF occurs. The ICD may deliver ineffective therapy or
tricyclic antidepressant toxicity. Many of these drugs have a fail to detect the arrhythmia. External shocks, when required,
characteristic known as use-dependency, such that their elec- should be delivered regardless of the presence of an ICD.
trophysiologic effect is greater at rapid heart rates. Slowing of The ICD recognizes VT or VF largely by the presence of a
the ventricular rate diminishes the toxicity. Thus, administra- heart rate that exceeds the programmed detection threshold.
tion of -adrenergic blockers can be helpful [27]. Supportive If an SVT exceeds the programmed rate threshold, the device
measures are required until the offending agent is excreted. will deliver an inappropriate therapy, either antitachycardia
pacing or an electrical shock [29]. Recurrent episodes can lead
to recurrent painful shocks. Occasionally antitachycardia pac-
WIDE QRS TACHYCARDIAS DUE ing for an atrial arrhythmia initiates VT (Fig. 41.11). Recurrent
inappropriate therapies can be managed by placing a magnet
TO VENTRICULAR CONDUCTION over the ICD pulse generator. This disables ICD arrhythmia de-
OVER AN ACCESSORY PATHWAY tection. It is important to recognize that VT or VF will also not
be detected with the magnet in place; external shocks will be
WCTs are also produced by conduction from atrium to ven- required to treat these arrhythmias. Use of a magnet to suspend
tricle over an accessory pathway in patients with the WPW detection is a temporary maneuver until the inciting arrhythmia

FIGURE 41.11. Tracings from a hospitalized patient who has an ICD are shown. From the top left,
atrial fibrillation with a rapid ventricular response is present. The rapid ventricular response is incorrectly
identified as ventricular tachycardia by the ICD and initiates a burst of antitachycardia pacing (ATP). ATP
initiates sustained ventricular tachycardia (VT). The VT rate is faster than the previous rate, which falls
into the programmed VF zone of the ICD, which then delivers a shock, restoring sinus rhythm. However,
atrial fibrillation recurred (not shown) repeatedly. Recurrent ICD therapies were interrupted by placing a
magnet over the ICD to suspend arrhythmia detection and treat the atrial fibrillation.
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436 Section III: Cardiovascular Problems and Coronary Care

can be brought under control or the ICD can be reprogrammed Patients with PVCs or NSVT who have relatively preserved
to allow better arrhythmia discrimination. left ventricular function do not usually need specific antiar-
Antiarrhythmic medications can have important interac- rhythmic therapy. Therapy with beta-blockers can be consid-
tions with ICDs [30]. These drugs can slow VT to a rate that ered for symptomatic patients. Rarely, other drugs are required
it is lesser than the detect rate of the ICD. VT is then not to control symptoms. Aggravating factors, such as electrolyte
detected or treated by the ICD. Antiarrhythmic drugs, par- abnormalities, should be sought and corrected. Therapy with
ticularly amiodarone, can increase the current required for class I AADs or sotalol is generally not indicated and may in-
defibrillation, such that the ICD no longer provides effective crease mortality [36,37].
defibrillation; in this setting, external shocks are required. Accelerated idioventricular rhythm (AIVR) is a wide-
complex ventricular rhythm at a rate faster than 40 beats per
minute and slower than 100 beats per minute and is usually
hemodynamically stable. The mechanism is probably related
NONSUSTAINED VT AND to enhanced automaticity. This rhythm often occurs in the first
VENTRICULAR ECTOPY: FIRST 12 hours following reperfusion of an acute myocardial infarc-
tion during periods of elevated sympathetic tone, and its onset
DO NO HARM is typically preceded by sinus slowing [38]. AIVR usually re-
solves without specific therapy; AAD treatment is rarely neces-
PVCs and NSVT (more than three ventricular complexes) are sary.
common in the ICU particularly associated with myocardial is- Digitalis-induced arrhythmias include ventricular ectopic
chemia, previous-healed myocardial infarction, and cardiomy- activity, an accelerated junctional rhythm, monomorphic VT,
opathies. Idiopathic PVCs also occur in some otherwise healthy or VF. Rarely, digitalis causes bidirectional tachycardia, in
patients, in whom they are of no consequence. The initial ap- which the QRS morphology alternates between two different
pearance of ventricular ectopy should prompt an evaluation morphologies; mortality is high if left untreated [39]. Patients
for possible aggravating factors (Table 41.3). Increasingly fre- with digitalis-induced VT should receive digoxin immune Fab
quent ectopy raises concern of increasing sympathetic tone pos- fragments (Digibind) [40].
sibly due to progression of the underlying illness. Treatment
should be directed at the underlying condition. Therapy with
-adrenergicblocking agents if not precluded due to hemody-
namic or pulmonary impairment is reasonable. Other antiar- OVERVIEW OF DRUGS
rhythmic agents should, in general, be avoided.
NSVT is a marker for increased sudden death risk in pa- COMMONLY USED FOR
tients who have had a prior myocardial infarction and in pa- MANAGEMENT OF VT/VF
tients with left ventricular hypertrophy [3133]. Patients with
an ejection fraction 40% or lesser and NSVT should be con-
IN THE ICU
sidered for electrophysiologic study. Those with inducible VT AADs (Table 41.4) are commonly grouped according to the
have a 9% per year risk of sudden death; ICDs are protective, Vaughan Williams classification scheme on the basis of whether
reducing total mortality from approximately 50% to 24% over their predominant action is to block sodium channels (class I),
5 years [34,35]. -adrenergic receptors (class II), potassium channels (class III),
or L-type calcium channels (class IV) [41]. Although this classi-
fication scheme is imperfect (many of the drugs affect multiple
channels or receptors), it remains in common use. The narrow
TA B L E 4 1 . 3 toxictherapeutic window and potential for proarrhythmia ne-
FACTORS AGGRAVATING VENTRICULAR cessitate use of AADs only when the potential risks are justi-
ARRHYTHMIAS IN HOSPITALIZED PATIENTS fied by the need to suppress an arrhythmia. For most drugs,
the initial dosing guidelines provide a starting point for drug
Acute myocardial ischemia and infarction administration. Titration to achieve the desired effect is often
required.
Transvenous catheter in the right ventricle mechanically Class I AADs block sodium channels with either intermedi-
inducing ectopic activity ate (IA), fast (IB), or slow (IC) onset and recovery of channel
Elevated sympathetic tone block during diastole. Class IC AADs such as flecainide and
Pain, anxiety moricizine increase long-term mortality in patients with coro-
Acute illness nary artery disease and depressed ventricular function [42,43].
Sympathomimetic agents (dobutamine, dopamine, Such agents are rarely used for VT in the ICU.
epinephrine, norepinephrine, milrinone, theophylline) Procainamide (IA) is a first-line agent for the treatment of
hemodynamically stable WCT, and as an alternative agent for
Hyperthyroidism
hemodynamically unstable WCT and VF. It is also a first-line
Hypoxemia agent for WCT due to the WPW syndrome. Procainamide is
Acid/base disturbance administered as an IV infusion at 20 to 30 mg per minute
up to a total initial dose of 17 mg per kg. The loading dose
Electrolyte disturbance may be followed by a maintenance infusion of 1 to 4 mg per
Hypokalemia minute. Procainamide has vasodilatory and negative inotropic
Hyperkalemia effects. Arterial blood pressure should be monitored carefully
Hypocalcemia during IV administration. It should be avoided in patients with
Hypomagnesemia depressed ventricular function (left ventricular ejection frac-
Drugs tion <0.40). In addition, NAPA, an active metabolite of the
QT prolongationtorsades de pointes (see Table 41.2) drug, exerts class III effects that can lead to prolongation of
Digitalis toxicity repolarization (increased QTc) and TDP. Serum levels of both
procainamide and NAPA should be monitored if the drug is
LWBK834-41
P1: OSO/OVY

TA B L E 4 1 . 4
DRUGS COMMONLY USED FOR VT/VF IN THE ICU (GROUPED BY VAUGHAN WILLIAMS CLASS AND OTHER)

IV dose
Antiarrhythmic Common
P2: OSO/OVY

Class drug indications Load Maintenance Contraindications Side effects Comments


LWBK834-Irwin/Rippe

IA Procainamide MVT, PMVT, 20 mg/min until 14 mg/min Hypotension, reduced EF, Hypotension, negative Active metabolite (NAPA)
WPW and AF, arrhythmia is CHF (reduce dosage in inotropism, follow Proc and NAPA
VF (second line) suppressed or side renal failure), proarrhythmia, levels Discontinue if
effects occur up to prolonged QT, lupus-like syndrome QRS widens by >50%
17 mg/kg total previous TDP
QC: OSO/OVY

IB Lidocaine Monomorphic VT, 1.01.5 mg/kg (additional 14 mg/min Seizure disorders, severe Seizures, status Appears to be most
polymorphic 0.75 mg/kg can be bradycardia or heart asthmaticus, effective during acute
VT/VF given as a second block, severe renal or hypotension myocardial ischemia
bolus) hepatic dysfunction
LWBK834-Irwin-v1.cls
T1: OSO

II -adrenergic PMVT/MVT Variable Variable Severe CHF; second- or Bradycardia, worsened Proven mortality benefit
blockers third-degree heart CHF, AV delay, in cardiac ischemia
block hypotension,
bronchospasm
III Amiodarone MVT, PMVT, VF 150 mg IV over 10 min 1 mg/min for Severe hepatic disease; Hypotension, multiorgan May be more effective
(may be repeated 6 h and then second- or third- toxicity (lung, liver, than lidocaine for
multiple times up to 5 mg/min degree heart block nervous system, eyes, most ventricular
2 g/24 h and 58 g skin, thyroid) arrhythmias
total)
Ibutilide AF (cardioversion), 1 mg IV (may repeat dose Prolonged QT interval, Torsades de pointes
WPW, and AF 10 min after initial electrolyte
dose) abnormalities
(hypokalemia,
hypomagnesemia),
polymorphic VT
Bretylium VT/VF (second line) 5 mg/kg (may repeat) 12 mg/min Severe renal failure Frequent late hypotension Removed from ACLS
treatment algorithms
due to limited supply

Sotalol VT/VF 1.01.5 mg/kg at Second- or third-degree Bradycardia, Not available
10 mg/min heart block hypotension, TDP intravenously in the
United States
Other Epinephrine Cardiac arrest 1 mg IV (repeated as 14 g/min
needed)
Vasopressin Pressor agent for 40 U IV (not repeated) Interchangeable with
cardiac arrest epinephrine
Magnesium Known low Mg+ , 12 g (may be repeated)
TDP

CHB, complete heart block; CHF, congestive heart failure; EF, ejection fraction; MVT, monomorphic VT; PMVT, polymorphic VT; TDP, torsades de pointes; VF, ventricular fibrillation; VT, ventricular
tachycardia; AF, atrial fibrillation; WPW, WolfParkinsonWhite.

437
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438 Section III: Cardiovascular Problems and Coronary Care

continued for longer than 24 hours. In addition to the QTc dial infarction have a risk of recurrent cardiac arrest or VT
interval, the width of the QRS complex should be monitored that exceeds 30% to 40%. ICDs effectively terminate recurrent
and the drug should be discontinued during initial loading or VT/VF and reduce mortality in these patients [4749]. Thus,
chronic therapy if the QRS widens by more than 50% of its sudden cardiac arrest survivors warrant evaluation after resus-
baseline value. citation and management of any intercurrent illness to assess
Lidocaine (class IB) is indicated for the acute management of the need for placement of an ICD and other arrhythmia ther-
life-threatening ventricular arrhythmias, especially in patients apy. Catheter ablation of VT is a valuable treatment option for
suspected of having acute myocardial ischemia. It can be ad- the control of recurrent arrhythmia. Therapeutic decisions are
ministered as 1.0 to 1.5 mg per kg IV bolus, which can be guided by the estimated risk of recurrence, underlying heart
repeated to a maximum bolus of 3 mg per kg, followed by an disease, functional status, and general prognosis.
infusion of 1 to 4 mg per minute. Unlike procainamide, lido-
caine has few adverse hemodynamic side effects. Its toxicity is
mainly due to neurologic side effects (seizures and tremors). Sustained Monomorphic VT
Beta-blockers (class II) antagonize the effects of -
adrenergic stimulation on the heart and have been shown to Sustained monomorphic VT is usually due to reentry through
reduce mortality in patients with depressed ventricular function a region of myocardial scar, most commonly from an old my-
or ischemic heart disease during chronic therapy [44,45]. They ocardial infarction. Myocardial scars causing VT also occur in
can be considered for hemodynamically significant or symp- cardiomyopathies, cardiac sarcoidosis, arrhythmogenic right
tomatic NSVT and PVCs, and for recurrent sustained ventricu- ventricular cardiomyopathy, and Chagas disease. In all of these
lar tachyarrhythmias in which elevated sympathetic tone is felt diseases, the substrate for the arrhythmia remains after resus-
to play a role. Negative inotropic effects, bradyarrhythmias, citation. The spontaneous recurrence rate exceeds 40% over
and aggravation of bronchospasm are major adverse effects. the following 2 years. Patients who present with sustained
Metoprolol, propranolol, atenolol, and esmolol are all avail- monomorphic VT, but have elevated cardiac enzymes indicat-
able for IV administration. Metoprolol can be given as a 5-mg ing infarction, should be presumed to remain at risk for VT
slow IV push and can be repeated every 5 to 10 minutes up to from reentry from a prior infarct scar. An ICD or long-term
a total of 20 mg IV or until the desired effect is obtained. On- therapy with amiodarone is generally considered after under-
going maintenance therapy can be administered as repeat IV lying myocardial ischemia and other aggravating factors are
boluses every 4 to 6 hours or through oral dosing. Esmolol has addressed. The underlying heart disease should be character-
a short half-life (2 to 9 minutes), making it useful when there ized; echocardiography and cardiac catheterization are often
is concern that a beta-blocker may be poorly tolerated, such warranted.
as in patients with hypotension or a history of bronchospasm.
Termination of the infusion is followed by rapid dissipation of Bundle Branch Reentry
effect.
Class III AADs cause prolongation of repolarization pri- Bundle branch reentry causes a unique form of monomorphic
marily by potassium channelblocking activity. This action is VT that results from a reentrant circuit utilizing the bundle
responsible for their antiarrhythmic and proarrhythmic (QTc branches as arms of the circuit. The reentry wave front typi-
prolongation and TDP) effects. cally circulates antegrade down the right bundle branch and
Amiodarone is usually classified as a class III agent, although up the left bundle branch, giving rise to a VT that has a left
it exhibits sodium, potassium, and calcium channel inhibition, bundle branch block QRS configuration. In patients with left
as well as -adrenergicblocking effects. It has excellent ef- bundle branch block in sinus rhythm, the VT can have the
ficacy in the management of ventricular arrhythmias and a same QRS morphology as sinus rhythm. This form of VT is
low incidence of proarrhythmia [46]. Amiodarone is a first- most commonly seen in patients with nonischemic dilated car-
line AAD option in the recently revised ACLS VF/pulseless diomyopathy [50]. Bundle branch reentry can be cured by ra-
VT algorithm [7]. Even though amiodarone causes QT pro- diofrequency ablation, but at least 25% of patients with this
longation, TDP is rare. IV amiodarone can be administered as form of VT will have other VTs as well [51]. Therefore, an ICD
150 mg bolus over 10 minutes, followed by a continuous in- is often recommended.
fusion at 1 mg per minute for 6 hours and then 0.5 mg per Rarely, sustained monomorphic VT occurs in a patient with-
minute. Additional 150 mg boluses can be given for break- out structural heart disease. The most common of these idio-
through arrhythmia up to a total load of approximately 2 g pathic tachycardias originates from a focus in the right ven-
per 24 hours and 5 to 8 g total. Amiodarone has a large and tricular outflow tract, giving rise to VT that has a left bundle
variable volume of distribution (averaging 60 L per kg) and branch block, inferior axis QRS configuration. VT is often cat-
long half-life (averaging 53 days). Major complications dur- echolamine sensitive and precipitated during exercise or phys-
ing IV administration are hypotension and bradyarrhythmias. iologic stress, occasionally emerging during other illnesses. Id-
When administered through a peripheral IV line, amiodarone iopathic VT rarely causes cardiac arrest, although hypotension
causes phlebitis; continuous infusions should be administered and syncope can occur [52]. Unlike other forms of VT, idio-
through a central venous catheter. During chronic long-term pathic VT is sometimes terminated with adenosine or vagal
therapy, hepatic toxicity, hyper- or hypothyroidism, pneumoni- maneuvers [53]. Beta-blocker and verapamil (especially in IV
tis, pulmonary fibrosis, neuropathy, tremor, and skin toxicity form) can also be effective at terminating and suppressing id-
are important concerns that require careful monitoring. iopathic VT [54]. Long-term therapy focuses on suppression
with beta-blockers or calcium channel blockers. Occasionally
catheter ablation is required [55].
LONG-TERM MANAGEMENT
AFTER RESUSCITATION FROM Polymorphic VTs
SUSTAINED VT/VF
Patients who have had TDP should be viewed as having a sus-
Patients with ischemic heart disease and reduced ventricular ceptibility to the arrhythmia. All known precipitants of TDP
function who are resuscitated from cardiac arrest or hemo- or QT prolongation should be avoided (Table 41.3). Patient
dynamically significant VT not attributable to acute myocar- should be provided with a list of these medications. Following
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Chapter 41: Ventricular Tachycardia 439

removal of aggravating factors, evaluation for possible con- TA B L E 4 1 . 5


genital long QT syndrome should be conducted. The diagnosis
is suggested by persistent QT prolongation and QT prolon- ADVANCES IN THE MANAGEMENT OF
gation on prior ECGs when potential offending drugs were VENTRICULAR TACHYCARDIA
absent and/or a family history of unexplained sudden death.
Long-term therapy and follow-up are required. Acute management involves assessment of hemodynamic
If the patient has a family history of sudden death and has status, ECG evaluation and diagnosis of ventricular
been resuscitated from PMVT, but the QT interval is normal, tachycardia versus supraventricular tachycardia with
other familial sudden death syndromes should be considered. aberrancy.
The Brugada syndrome is a unique familial cause of sudden Immediate cardioversion should be provided for
cardiac death that accounts for some cases of idiopathic VF hemodynamically unstable VT.
[56]. Patients with this syndrome have a baseline ECG with Reversible causes of VT (e.g., ischemia, electrolyte
RBBB, ST-segment elevation in leads V1 to V3 and no evidence abnormalites) should be identified and treated.
of structural heart disease [57]. Catecholaminergic polymor- Antiarrhythmic drugs should be considered when initial
phic ventricular tachycardia (CPVT) is an inherited primary attempts at cardioversion are unsuccessful or when VT
electrical disorder of the heart associated with a high rate recurs.
of sudden death [58,59]. Autosomal-dominant mutations of Long-term management may include consideration for an
the ryanodine receptor account for the majority of cases, but implantable defibrillator in appropriately selected patients.
autosomal-recessive mutations of calsequestrin have also been
reported [59]. These patients frequently present at an early age
with stress-induced syncope or sudden cardiac arrest. The rest-
ing ECG is usually unremarkable, and both invasive and non-
invasive testing fail to reveal signs of structural heart disease.
Exercise testing often demonstrates runs of PMVT during ex- Cardiac Arrest of Unclear Cause
ercise frequently with a beat-to-beat 180-degree rotation of the
QRS axis (bidirectional tachycardia) [58]. Genetic testing can Often the cause of a cardiac arrest cannot be determined with
aid in the diagnosis. Beta-blockers titrated to maximal doses certainty. The patient resuscitated from VF who has enzymatic
are the mainstay of therapy for CPVT [58]. An ICD may be evidence of nonQ-wave myocardial infarction, but depressed
warranted for treatment of patients with these syndromes. ventricular function and evidence of a prior myocardial infarc-
PMVT due to acute myocardial infarction usually occurs in tion might have suffered VT from reentry in the old infarct scar
the first hour of the infarction and is unusual after initial re- or an ischemic arrhythmia. Treatment for ischemia and an ICD
suscitation. Recurrent episodes should prompt assessment for is often considered.
ongoing ischemia. The risk of recurrent cardiac arrest is sim- A summary of advances in the management of VT, based on
ilar to that for patients with a similar-size infarction without randomized controlled trials or meta-analyses of such trials, is
cardiac arrest. given in Table 41.5.

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Chapter 42: Supraventricular Tachycardias: Recognition and Management in the Intensive Care Setting 441

CHAPTER 42 SUPRAVENTRICULAR
TACHYCARDIAS: RECOGNITION AND
MANAGEMENT IN THE INTENSIVE
CARE SETTING
AMMAR HABIB, JOSEPH J. GARD, TRACI L. BUESCHER AND SAMUEL J. ASIRVATHAM

ular (AV) conduction block, it manifests as an irregular tachy-


OVERVIEW AND CLASSIFICATION cardia and may be confused with AF. Junctional tachycardia is
also a rare regular narrow complex tachycardia that is typically
Supraventricular tachycardias (SVTs) are frequently encoun- self limited and very unusual in the adult intensive care patient
tered in the intensive care unit (ICU) setting [1]. Although gen- population.
erally considered benign, in the context of the critically ill pa- These tachycardias may be of sudden onset and abrupt ter-
tient, SVTs can be particularly problematic, complicating care mination (AVNRT, AVRT) or may occur and dissipate gradu-
and at times, contributing to patient morbidity and mortality. ally (sinus tachycardia, automatic atrial tachycardia). A useful
Atrial fibrillation (AF) and macroreentrant atrial tachycar- further distinguishing electrocardiographic feature within this
dias are the most common SVTs observed in ICU practice. subset of SVTs is the RP interval. First, a careful search for the
However, regular reentrant tachycardias such as atrioventricu- P wave should take place. If the P wave is recognized, it should
lar node reentry (AVNRT) may be initiated or exacerbated by be determined whether it occurs closer to the preceding QRS
the stress of critical illness or the use of adrenergic agents. or to the succeeding QRS complex. If the P wave occurs closer
The intensive care provider should be familiar with the com- to the succeeding QRS (long RP tachycardia), sinus tachy-
mon varieties of SVTs and have an approach developed to cardia and atrial tachycardia should be considered (Fig. 42.2).
quickly diagnose the exact arrhythmia (Fig. 42.1). Such diagno- When the P wave is closer to the preceding QRS (short RP
sis is essential in the formulation of a management plan for the tachycardia), AVNRT or AVRT are likely although important
treatment of acute events as well as prevention of recurrence. exceptions exist [24].
Although several approaches for the diagnosis of SVT have The P wave morphology may also be useful in determining
been described, in the context of the critically ill patient, the the mechanism of arrhythmia. The P wave in sinus rhythm (up-
use of easily recognized parameters aids quick diagnosis and right in leads II, III, and aVF and biphasic in lead V1 ) is easily
thus prompt institution of a management plan. In most sit- recognized. When an abrupt change in the P wave morphol-
uations, three criteriaregularity of the tachycardia (regular ogy occurs regardless of the heart rate, a nonsinus mechanism
or irregular), QRS width (narrow complex or wide complex), including atrial tachycardia should be suspected (Fig. 42.3).
and, when relevant, measurement of the RP interval (interval
between the preceding QRS complex and a recognized P wave
during tachycardia) provide sufficient data for accurate diag-
nosis.
In this chapter, regular narrow complex tachycardia is Sinus Tachycardia
addressed first, followed by the more common irregular tachy-
cardias. Each category includes a description of the pathogene- Metabolic stress commonly encountered in the critically ill pa-
sis, electrocardiographic recognition, and general principles of tient often causes increased automaticity of the sinus node, pro-
management of the common varieties. Because of the frequency ducing a regular narrow complex tachycardia. Other causes of
of occurrence of AF, this arrhythmia is discussed in relatively sinus tachycardia in the critical care setting include adminis-
more depth. For each section, emphasis is placed on points of tration of adrenergic medications, hypovolemia, and inflam-
interest designed to specifically assist the caregiver for critically mation. Sinus tachycardia is characterized on ECG by regular
ill patients. PR interval and a uniform P wave morphology that is upright
in leads II, III, and aVF. Ventricular rate typically ranges from
100 to 140 beats per minute with gradual variation in response
to the underlying clinical condition or therapeutic intervention.
REGULAR NARROW COMPLEX Sinus tachycardia is often a normal physiologic response to
TACHYCARDIA underlying systemic illness. Treatment of the underlying cause
usually helps slow down the heart rate. At times, however,
When a regular narrow complex tachycardia (QRS duration the increased heart rate (albeit a physiologic response to some
<120 milliseconds) is observed, several important arrhythmias other stress) may itself be detrimental. For example, in patients
should be considered in the differential diagnosis. These include with critical coronary disease, rapid sinus rates may give rise to
sinus tachycardia, AVNRT, atrioventricular reentrant tachycar- an acute ischemic syndrome and possible ventricular arrhyth-
dia (AVRT) using an accessory pathway (AP), and automatic mia. Similarly, in conditions such as critical mitral stenosis and
atrial tachycardia. Each of these arrhythmias is discussed in severe diastolic dysfunction, rapid rates are detrimental as dias-
more detail in the text to follow. Atrial flutter may present as a tolic filling times need to be maximized. In these circumstances,
regular tachycardia, but often because of variable atrioventric- temporary use of beta-blockers or calcium channel blockers
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442 Section III: Cardiovascular Problems and Coronary Care

can decrease heart rates while the primary cause of the sinus
tachycardia is being investigated.
Automatic atrial tachycardias are very similar in occurrence
to sinus tachycardia in the intensive care setting. They are fre-
quently seen in patients in shock, under stress, or on high doses
of beta-adrenergic agents (epinephrine, high-dose dopamine).
They can be readily distinguished from sinus tachycardia by
close analysis of the P wave morphology. Unlike sinus tachycar-
dia, however, these arrhythmias are not always a result of a per-
sistent underlying abnormality (blood loss, hypoxia, etc.) and
may be a primary cause of functional deterioration in a given
patient [5,6]. Sodium channel blockers (class I antiarrhythmic
agents) can be used for both acute termination and prevention
of recurrences [79]. Typically, however, treatment of the un-
derlying problem and decreasing the use of intravenous sym-
pathomimetics is sufficient to prevent recurrence in patients
who have developed atrial tachycardia in the setting of critical
illness.

FIGURE 42.1. Narrow complex tachycardias in the intensive care


unit. The most common regular narrow QRS tachycardias are atri-
oventricular node reentry, accessory-pathway related tachycardia, and
Specific Considerations in the
automatic tachycardias such as sinus tachycardia and atrial tachycar- Intensive Care Unit
dia. These arrhythmias can be readily differentiated in most cases with In patients who are continuously monitored, sinus tachycardia
careful analysis of the electrocardiogram. A long RP tachycardia (right
can often be diagnosed by looking at the transition from normal
panel) where each P wave is closer to the succeeding rather than the pre-
ceding QRS is characteristic of sinus tachycardia and atrial tachycardia. heart rates to the present rate of tachycardia. For example, if
In tachycardias where an extranodal accessory pathway is used for ret- the patient has a regular long RP tachycardia at 170 beats per
rograde conduction (orthodromic reciprocating tachycardia, ORT), a minute, all intervening rates from the baseline rate (100, 110,
short RP interval is seen with an easily discernible retrograde P wave. 130, 150 bpm, etc.) will be seen and demonstrate gradual onset
With AV node reentry (left panel), because AV activation proceeds from of the tachycardia with progressively faster rates and a reverse
a common turnaround point in or near the AV node, the R wave and P pattern of resolution.
wave may be nearly simultaneous producing a very short RP interval If an abrupt increase in heart rate is noted, a non-sinus
and difficult to discern P wave (see text for details). mechanism should be suspected. However, some critically ill

FIGURE 42.2. Patient with initially regular SVT than with a change in ventricular response rate. The
underlying supraventricular arrhythmia is an atrial tachycardia (automatic or macroreentrant). Note the
differences in P wave morphology to sinus rhythm with negative P waves in the inferior leads and all
positive P wave (not biphasic) in lead V1 . The abrupt changes in ventricular responses may exacerbate
symptoms especially in patients already compromised with critical illness.
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Chapter 42: Supraventricular Tachycardias: Recognition and Management in the Intensive Care Setting 443

FIGURE 42.3. 12-Lead electrocardiogram of typical atrioventricular node reentry (AVNRT). The P waves
are readily recognized just following the QRS complex. The regular tachycardia with short RP interval
should raise suspicion for this arrhythmia. The P waves are typically very narrow in AVNRT as a result
of the early septal activation during this tachycardia. AV nodal blockade will terminate the arrhythmia
and likely prevent recurrence. This arrhythmia may be hemodynamically poorly tolerated even when rel-
atively slow because of the near simultaneous atrioventricular activation. This results in atrial contraction
against a closed atrioventricular valve producing increased back pressure in the venous beds (systemic and
pulmonary).

patients develop inappropriate sinus tachycardiaa disorder proceeds more rapidly in the fast pathway and is responsible
of the autonomic control of the sinus node that results in P for the normal PR interval and conduction to the ventricle.
wave morphology identical to sinus rhythm but with abrupt Retrograde penetration of the slow pathway occurs and pre-
and frequent increases in the heart rate for no apparent or de- vents the antegrade wave front through the slow pathway from
finable reason [1012]. Inappropriate sinus tachycardia may reaching the AV node. Consequently, slow pathway activation
also be associated with other features of autonomic dysfunc- remains electrically silent. When a premature atrial beat oc-
tion and contribute to hypotension. Persistent tachycardia can curs, block in conduction down the fast pathway (relatively
be a feature of this condition, especially when patients recover shorter refractory period) allows antegrade conduction with a
from catastrophic illness. long PR interval down the slow pathway. From this site, retro-
grade activation of the fast pathway may now occur and the
reentrant arrhythmia ensues. Accordingly, the typical electro-
Atrioventricular Nodal Reentry Tachycardia cardiographic feature of initiation of AVNRT is a premature
atrial contraction with a long PR interval followed by the sud-
AVNRT is a common arrhythmia in the ICU and the most com- den onset of a regular narrow complex tachycardia with a very
mon form of regular SVT, accounting for approximately 60% short RP interval.
of cases [1,13]. It is more common in female patients between AVNRT is characterized on ECG by a regular narrow com-
the ages of 20 and 40 years. Patients may complain of palpita- plex tachycardia with P waves buried within or appearing ei-
tions that occur with sudden onset and resolve spontaneously ther just before or after the QRS complex. The P wave is often
[14]. In addition, some patients may experience the urge to mic- closer to the preceding QRS complex, giving rise to a short RP
turate either during or after termination of the rhythm. Older tachycardia. The RP interval reflects the time from ventricular
and debilitated patients may have severe symptoms in addition activation to atrial activation and is short in AVNRT because
to the palpitations including angina and syncope. of the rapid conduction of the impulse retrograde to the atrium
AVNRT is a reentrant tachycardia that has a complex cir- via the fast pathway. Short RP tachycardias signify fast ret-
cuit. The atrial myocardial inputs to the AV node are discrete, rograde activation that is characteristic of AVNRT. Ventricu-
involving an anterior input called the fast pathway and a pos- lar rate is often noted to be between 150 and 250 beats per
terior input in the region of the coronary sinus (CS) called the minute.
slow pathway. Because of these discrete inputs, in some pa- Acute management of symptomatic AVNRT often begins
tients, there is sufficient disparity in the conduction times and with attempts at Valsalva-like maneuvers which increase vagal
refractory periods of the two pathways, allowing initiation and tone and influence pathway refractoriness. If these are effective,
maintenance of a reentrant tachycardia (AVNRT) [1517]. no further therapy is usually required [18]. Medical therapy is
In sinus rhythm, there is near simultaneous antegrade con- indicated in patients with continued symptoms. Adenosine may
duction through both the fast and slow pathway. Conduction be used as a first-line treatment and invariably terminates the
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444 Section III: Cardiovascular Problems and Coronary Care

tachycardia. Other agents that may be used in the acute set-


ting include intravenous (non-dihydropyridine) calcium chan-
nel blockers like verapamil or diltiazem. Beta-blockers and
digoxin, like calcium channel blockers, may be used to
slow conduction within the AV nodal system to interrupt
reentry.

Specific Considerations in the Intensive Care Unit


Patients will typically have a history of AVNRT with symp-
tomatic episodes in the setting of critical illness resulting from
catecholamine stress and frequent premature atrial beats that
initiate reentry. Repeated episodes may occur that result in
hemodynamic instability. Once the diagnosis is established, it
is important that cardioversion not be considered as primary
management of this arrhythmia since recurrence is likely and
simpler measures to terminate the arrhythmia exist. Any AV
nodal blocking agent will terminate the arrhythmia (adenosine,
esmolol, metoprolol, verapamil, etc.). A short-acting agent like
adenosine may be tried first. If immediate reappearance is ob-
served, intravenous infusion of an AV nodal blocking agent
can be initiated and titrated both for blood pressure control
as well as prevention of recurrence. Rarely, patients will have
FIGURE 42.4. When an extranodal accessory pathway is present, the
incessant AVNRT compromising their care. Anti-arrhythmic most common arrhythmia is ORT (orthodromic reciprocating tachy-
agents or urgent radiofrequency ablation can be considered in cardia). Conduction occurs down the normal AV conduction system
those situations. and up the accessory pathway producing a short RP tachycardia with
an RP interval typically more than 100 ms.

Atrioventricular Reentry Tachycardia


tachycardia, it may be difficult to distinguish this rhythm from
AVRT is caused by a reentrant circuit that involves both the AVNRT or atrial tachycardia (discussed later). Termination of
AV node and an extranodal AP. APs are typically muscular this rhythm usually transpires secondary to AV nodal conduc-
connections that traverse the AV annulus connecting atrial and tion fatigue, increased vagal tone, or a premature extrasystolic
ventricular myocardium directly, thus bypassing the AV node beat.
[1921]. Antidromic tachycardia manifests as a regular wide com-
There are several manifestations with APs that may result plex tachycardia and can occur in patients with antegrade con-
in electrocardiographic changes and arrhythmia in the inten- ducting APs [22,23] (Fig. 42.7). This variant is less common but
sive care setting. In sinus rhythm, when the AP conducts in an important to recognize since it may be confused with ventric-
antegrade direction, a typical constellation of electrocardio- ular tachycardia. Initiation typically occurs with a premature
gram (ECG) findings result. The early part of the QRS is ab- atrial contraction that blocks in the AV node. Antegrade con-
normal ( wave) because of preexcitation of the ventricular my- duction proceeds via the AP to the ventricle with the return
ocardium rather than depolarization via the usual infrahisian
conduction system. The combination of a short PR interval in
addition to the wave enables ECG diagnosis of preexcita-
tion. WolffParkinsonWhite (WPW) syndrome results when
reentrant tachycardia occurs in the presence of this pattern of
preexcitation.
Reentrant tachycardias include those with antegrade con-
duction down the AV node and up the AP (orthodromic-
reciprocating tachycardia) and the inverse circuit with ante-
grade conduction down the AP and retrograde conduction
up the AV node (antidromic tachycardia). Finally, preexcited
atrial fibrillation is a potentially life-threatening arrhythmia,
the recognition and management of which is discussed in the
text to follow (Figs. 42.442.6).
AVRT is a reentrant narrow complex tachycardia like
AVNRT. Patients with AVRT have an AP that allows conduc-
tion to bypass the AV node. An impulse, either a premature
atrial contraction or a premature ventricular contraction, trav-
els to the AV node through the bundle of His, activating the
ventricular system. Subsequently, the propagation travels up
the AP causing retrograde conduction back to the atrium. This
circuit is known as orthodromic AVRT because the antegrade
pathway conducts the impulse to the ventricles via the normal
FIGURE 42.5. When an extranodal accessory pathway is present, a
AV node and HisPurkinje system. Orthodromic AVRT gen- regular wide complex tachycardia may also result. Here, the tachy-
erally has a narrow QRS complex but may have a wide QRS cardia circuit proceeds antegrade down the accessory pathway and up
complex when there is an underlying bundle-branch block. The through the AV nodal conduction system producing a regular wide
ventricular rate continues to be controlled by the AV node dur- QRS tachycardia with the QRS morphology dependent on the site of
ing orthodromic AVRT. Because it is a regular narrow complex the accessory pathway. ART, antidromic-reciprocating tachycardia.
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Chapter 42: Supraventricular Tachycardias: Recognition and Management in the Intensive Care Setting 445

limb of the circuit through retrograde AV nodal conduction.


Both orthodromic and antidromic AVRT are dependent on AV
nodal conduction, and thus, AV nodal blockade (adenosine,
beta-blockers, etc.) will terminate the arrhythmia and prevent
recurrence. In contrast, a preexcited tachycardia occurs when
another SVT (independent of the pathway) such as sinus tachy-
cardia, AF, atrial flutter, etc., arises, but because of the presence
of the antegrade conducting AP, rapid conduction to the ventri-
cle takes place, bypassing the AV node. For these arrhythmias,
AV nodal blockade would be contraindicated as there would be
promotion of rapid aberrant conduction via the AP predispos-
ing to ventricular arrhythmias. This is particularly problematic
during AF when direct conduction through the antegrade AP
may lead to ventricular fibrillation. The 2003 American College
of Cardiology/American Heart Association (ACC/AHA) SVT
management guidelines indicated that the incidence of sudden
death with WPW is increased in patients with a minimum R-
R interval <250 milliseconds during AF (regardless of whether
AF is spontaneous or induced), a history of symptomatic tachy-
FIGURE 42.6. Potential life-threatening arrhythmia seen in patients cardia, multiple APs, and Ebsteins anomaly [24].
when extranodal accessory pathway is preexcited atrial fibrillation. The acute management of regular tachycardia in patients
The AV node normally protects the ventricle from rapid ventricular with APs (orthodromic or antidromic AVRT) is similar and
rates during atrial fibrillation. However, when an accessory pathway consists of AV nodal blockade to terminate the arrhythmia and
is present, conduction may proceed down the accessory pathway as
the use of longer-term beta-blockers or calcium channel block-
well as the AV node producing extremely rapid ventricular rates. The
characteristics of a preexcited AF electrocardiogram include irregularly ers to prevent recurrence. AV nodal blocking therapy is often
irregular R-R intervals along with rapid rates and importantly, irregular sufficient as a temporizing maneuver until the patients critical
QRS duration and morphology as well (see text for details). illness subsides and definitive ablation therapy can be offered
[25,26].

FIGURE 42.7. Regular wide complex tachycardia. When a regular wide complex tachycardia is seen
in the critical care setting, ventricular tachycardia should always be considered. However, if the baseline
electrocardiogram shows preexcitation, an antidromic tachycardia can be diagnosed and easily terminated
with any AV nodal blocking agent. If the baseline electrocardiogram is not available, wide QRS tachycardia
with consistent 1:1 RP association in the absence of structural heart disease should raise suspicion for
an accessory pathway-mediated mechanism.
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446 Section III: Cardiovascular Problems and Coronary Care

Acute Management of Hemodynamically Procainamide may chemically convert the patient from AF to
Significant AVRT sinus rhythm and in addition, suppress conduction via the AP.
Patients with AVRT should be referred to a cardiac elec-
Valsalva-like maneuvers that increase vagal tone may be at- trophysiologist for possible radiofrequency catheter ablation.
tempted initially. As with acute treatment of AVNRT, adeno- Catheter ablation is highly successful, is associated with low
sine may be used as a first-line agent for medical management. risk, and eliminates the need for long-term drug therapy [32].
Because of its very short half-life, a trial of adenosine may be at- Ablation is often considered first-line therapy in young patients
tempted in patients with tenuous hemodynamics prior to emer- who prefer a curative approach.
gent cardioversion. However, adenosine may potentially cause
increased atrial vulnerability, a serious proarrhythmic side af-
fect [27,28]. An alternative category of drugs often adminis-
Specific Considerations for the Intensive Care Setting
tered in the acute setting for treatment of orthodromic AVRT Preexcited AF should be immediately recognized and treated
includes intravenous calcium channel blockers. Intravenous ve- when observed but is an unusual presentation in critically ill pa-
rapamil may be used and repeated every 2 to 3 minutes for tients. More commonly, repeated episodes of reentrant AVRT
acute termination of orthodromic AVRT but may be relatively (usually orthodromic) arise in patients with known APs. Fre-
contraindicated in patients with significant hypotension or de- quent and sometimes incessant episodes can result from the
pressed ventricular function or heart failure. Additional agents stress of critical illness combined with possible discontinua-
that may be used and often considered second-line treatment tion of previously used AV nodal blocking agents for medical
include intravenous beta-blockers (like metoprolol and pro- management. Judicious use of short-acting intravenous beta-
pranolol) and procainamide. Rather than having a direct effect blockers will help prevent recurrences of arrhythmia without
on AV nodal conduction, procainamide acts on the atrial and major untoward hemodynamic consequences.
ventricular myocardium, causing decreased conduction and in- Caregivers of the critically ill patient must also be aware that
crease refractoriness of APs and the HisPurkinje system. the presence of a WPW pattern on the EKG by itself is not a
In contrast, when an irregular wide complex tachycardia contraindication to use beta-blockers or other AV nodal block-
is noted in a patient with known WPW, urgent intervention ing agents if clinically required for comorbid illnesses such as
is required [2931]. Preexcited AF once recognized, should be coronary disease. If, however, a patient with WPW has AF, AV
immediately terminated (Fig. 42.8). If the patient is hemody- nodal blocking agents should be avoided or used in conjunc-
namically unstable, urgent cardioversion is required. If not, tion with antiarrhythmic agents like procainamide to suppress
an antiarrhythmic agent such as procainamide can be used. AP conduction (Fig. 42.9).

FIGURE 42.8. Preexcited atrial fibrillation. All caregivers for critically ill patients should be familiar with
this pattern. An irregular wide complex tachycardia is noted. Importantly, the ventricular rates are fast,
and each QRS morphology is slightly different. Especially if the baseline electrocardiogram had shown
preexcitation (WPW) pattern, this urgent condition of preexcited atrial fibrillation should be immediately
recognized. Regardless of present symptoms, cardioversion should be considered if the patient is relatively
unstable; chemical cardioversion with an agent such as procainamide that may convert the atrial fibrillation
to sinus rhythm and simultaneously slow conduction to the accessory pathway can be tried.
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Chapter 42: Supraventricular Tachycardias: Recognition and Management in the Intensive Care Setting 447

FIGURE 42.9. Characteristic electrocardiogram in patient with antegrade preexcitation. Note the short
PR interval and the wave clearly seen in the lateral precordial leads and lead II. The R wave seen in
lead V1 and negative wave in lead I is consistent with the left-sided accessory pathway. If a patient with
this baseline electrocardiogram develops atrial fibrillation, this should be treated as a medical emergency
because of risk of ventricular fibrillation from the atrial fibrillatory waves conducting to the ventricle via
this pathway without the intervening protective effects of the AV node.

IRREGULAR NARROW COMPLEX important clinically because of the increased risk of hemody-
namic instability and mortality associated with this arrhyth-
TACHYCARDIA mia in the intensive care setting. AF is characterized by irregu-
lar atrial contractions, as demonstrated on ECG by irregularly
Several of the regular narrow complex tachycardias already dis- irregular f waves that may manifest as continuous irregular
cussed may occasionally present with irregular R-R intervals. variation in the baseline (Fig. 42.10).
However, by far, the most common irregular narrow complex AF may become problematic to patients in the intensive care
tachycardia occurring in an ICU setting is AF. In this section, setting due to hemodynamic instability. Hemodynamic com-
we discuss this common arrhythmia in detail, presenting in- promise is likely in cases of AF associated with rapid ventric-
formation on pathogenesis, recognition of variants, and acute ular response, especially when associated with diastolic dys-
management in the critically ill patient. Although less com- function. In addition, hemodynamic instability is common in
mon, atrial flutter with variable conduction block and multi- AF with rapid ventricular response in patients in whom a more
focal atrial tachycardia should be distinguished from AF since prolonged diastolic filling period would be desirable, such as
management differs significantly. mitral stenosis, hypertrophic obstructive cardiomyopathy, re-
strictive cardiomyopathy, or constrictive pericardial disease.
Patients with underlying WPW syndrome who develop AF can
Atrial Fibrillation have hemodynamic instability due to a rapidly conducting an-
tegrade AP as previously mentioned. If antegrade AP conduc-
AF is the most common type of arrhythmia, and the most com- tion is present during AF, ECG findings show an irregular wide
mon SVT seen in the ICU. Incidence increases with age; it is complex tachycardia with varying degrees of ventricular pre-
found in less than 0.1% of adults younger than 55 years but in excitation. As mentioned previously in the discussion of AVRT
more than 9% of the population age 80 years or older [33,34]. management, AV nodal blocking agents are contraindicated in
AF is characterized by the presence of chaotic appearing mul- this instance as they may enhance antegrade AP conduction
tiple shifting reentrant atrial wavelets that may appear flat or and increase risk of ventricular fibrillation.
irregular. Classification of AF usually depends on the dura- Another important complication of AF is thrombus forma-
tion and frequency of occurrence. Paroxysmal AF makes up tion in the left atrium that may embolize to the cerebral cir-
about 40% of cases and may last up to 7 days, terminating culation and ultimately result in ischemic stroke. Therefore,
spontaneously. Nonparoxysmal AF lasts more than 7 days and early recognition of AF, its risk factors, and proper treatment
requires cardioversion for termination. Identification of AF is is prudent in the management of the critically ill patient.
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448 Section III: Cardiovascular Problems and Coronary Care

FIGURE 42.10. Atrial fibrillation with rapid ventricular rates. In some leads, there is an appearance of
organization of the arrhythmia (flutter-like). However, this is inconsistent in other leads and is often seen
in atrial fibrillation, particularly in patients with left atrial hypertrophy. The ventricular rates are irregular
and management will depend on the associated hemodynamic changes (see text for details).

Causes of Atrial Fibrillation or remodeling due to cardiomyopathy [42]. Other cardiac risk
factors include pericarditis, myocarditis, congenital heart dis-
Initiation and maintenance of AF varies and often is multi-
ease, and valvular heart disease. Obesity and metabolic syn-
factorial. The three main initiating causes include rapidly dis-
drome have also been linked to AF [43]. Pulmonary embolism
charging triggers or foci, the autonomic nervous system that
is also a risk factor for AF and should never be overlooked in
triggers activity, and substrate abnormalities that permit and
the intensive care or postoperative setting. Consumption of ex-
promote wavelet reentry [3537]. The pulmonary veins are
cessive amounts of alcohol is a well-known risk factor for AF.
lined with myocardium that has a shorter effective refractory
Binge drinkers have a significantly increased risk of developing
period and is capable of more rapid discharge than the endo-
AF, a phenomenon referred to as holiday heart syndrome [44].
cardium. The muscular lining of the pulmonary veins is the
Moderate use of alcohol, in contrast, has not been consistently
most common site of rapid discharge leading to the initiation
shown to be associated with AF [45]. Surgery, both cardiac and
and maintenance of AF. The autonomic nervous system is also
noncardiac is also associated with the development of AF. Car-
an important source in initiating AF. Sympathetic stimulation
diac surgeries, especially coronary artery bypass grafting and
may facilitate altered automaticity and result in focal discharge.
valvular repair or replacement, have a greater association with
In addition, enhanced vagal tone may shorten the refractory pe-
the development of AF than noncardiac surgeries. Periopera-
riod and increase heterogeneity. Patients with conditions like
tive administration of beta-blockers for prophylactic treatment
myocarditis, congestive heart failure, valvular heart disease,
has been shown to significantly reduce the incidence of AF in
coronary artery disease, hypertension, and other diseases lead-
this setting [46,47]. Additional noncardiac risks factors asso-
ing to atrial stretch and interstitial fibrosis may develop AF due
ciated with AF include obstructive sleep apnea, thyrotoxicosis,
to these substrate abnormalities. Substrate abnormalities cause
and inflammatory states.
heterogeneity in electrophysiologic cellular properties leading
AF is common in the surgical perioperative period (predom-
to breakdown in waveform propagation and multiple wavelet
inantly in the first 4 postoperative days), and as previously
reentry. Because of electrical remodeling, the more frequent
mentioned, most often observed in patients undergoing cardiac
AF occurs, the greater the likelihood of further AF episodes
surgery. Studies have reported that AF may occur in up to 40%
[38,39].
of patients undergoing coronary artery bypass grafting and
In addition, several reversible risk factors have been identi-
up to 60% in those undergoing combined coronary grafting
fied to be associated with AF, and these should be recognized
and valve surgery [4850]. Postoperative AF may be reduced
by the practitioner to aid in proper management. The most
by administration of prophylactic doses of beta-blockers, cal-
common underlying disease that may lead to AF is hyperten-
cium channel blockers, amiodarone, corticosteroids, or even
sion [40]. Studies have shown that treatment of hypertension
lipid-lowering agents [5154]. The increased incidence of AF
with ACE inhibitors or ARBs may reduce the incidence of AF,
in the perioperative setting is unknown but thought to be sec-
especially in patients with altered left ventricular function [41].
ondary to atrial ischemia, atrial incisions, pericarditis, inflam-
The utilization of beta-blockers is also effective in controlling
mation, changes in autonomic tone, and large fluid shifts. Im-
ventricular response. AF has been associated with up to 10% of
portant risk factors for the development of AF postoperatively
patients suffering from an acute myocardial infarction. The un-
include cessation of beta-blocker therapy, chronic obstructive
derlying mechanism is thought to be secondary to atrial stretch
pulmonary disease, left atrial enlargement, advanced age, heart
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Chapter 42: Supraventricular Tachycardias: Recognition and Management in the Intensive Care Setting 449

failure, and a previous history of AF. Atrial fibrillation in this gies to the patients needs is important in management of AF.
setting is self-limited and usually resolves completely within 8 Although treatment strategies may vary, elderly patients who
weeks. have minimal symptoms are often managed with rate control,
whereas younger patients with significant symptoms and struc-
tural heart disease are often managed with rhythm control.
Management of Atrial Fibrillation
The goal of AF treatment is to minimize symptoms (palpi- Specific Considerations for the Intensive Care Setting. In all
tations, shortness of breath, lightheadedness, dizziness, and patients with AF, systematic consideration to whether rate or
fatigue), prevent or reduce tachycardia-induced cardiomyopa- rhythm control strategies should be adopted, and a decision as
thy, and prevent thromboembolic complications like stroke. to which anticoagulation strategy is most appropriate should
Whether treatment of AF results in favorable outcomes is un- be made. In the critically ill patient, timely judgment regarding
known. Although the Framingham study showed increased treatment with either urgent control of rate or rhythm becomes
incidence of mortality in patients with AF after adjustment more crucial. In addition, a careful analysis of the potential
for common confounders, other, more recent studies have not risks associated with slowing of the heart rate or the devel-
shown that treatment contributes to improved survival rates opment of proarrhythmic complications from antiarrhythmic
[55]. However, as with all other arrhythmias, it is prudent therapy is needed.
to evaluate and assess the hemodynamic stability of a patient Atrial fibrillation with obvious hemodynamic collapse re-
with AF. As mentioned previously, critically ill patients may quires urgent cardioversion regardless of anticoagulation sta-
develop hemodynamic instability in association with AF, espe- tus, attempts at rate control, etc. This situation is quite rare.
cially those for whom a shortened diastolic filling period would Whenever significant hemodynamic compromise is noted in a
be detrimental (e.g. mitral stenosis, hypertrophic obstructive patient with AF (particularly with reasonably controlled rates),
cardiomyopathy, restrictive cardiomyopathy, constrictive peri- another cause for hypotension or shock should be investigated.
carditis) or WPW. In these instances, synchronized direct cur- However, in patients with significant valvular disease (critical
rent (DC) cardioversion is indicated. Premedication with an aortic stenosis) or with severe diastolic ventricular dysfunc-
anxiolytic, opiates, or generalized anesthesia is appropriate. tion (longstanding hypertension, hypertrophic cardiomyopa-
DC cardioversion usually results in successful conversion to thy), the onset of AF can be very symptomatic and occasionally
normal sinus rhythm in a majority of cases. Treatment with lead to hypotension, pulmonary edema, and findings consistent
intravenous procainamide or ibutilide may also be used in pa- with cardiogenic shock.
tients with AF and a wide-complex tachycardia associated with Nevertheless, in most situations, the clinician should assess
hemodynamic instability as these patients may have underlying systematically for optimal methods to control rate, and if symp-
WPW. Eventually, patients with AF in the setting of underlying toms continue despite rate control, methods to restore sinus
WPW should undergo radiofrequency ablation of the AP once rhythm and assess for anticoagulation are needed.
deemed clinically suitable.
In hemodynamically stable patients, a more conservative Rate Control
management approach is taken. Once the patient is considered
to be hemodynamically stable, a history and physical exam- Rate control for patients with AF is often pursued not only to
ination focusing on delineating a possible reversible cause of help alleviate symptomatic palpitations, but also to prevent
AF should be undertaken. Common, reversible causes of AF hemodynamic compromise and prevent tachycardia-induced
in the critically ill patient include myocardial infarction, peri- cardiomyopathy that may occur with prolonged rapid ventric-
carditis, infection or inflammation, pulmonary embolism, hy- ular rates. Rate control provides adequate ventricular filling
perthyroidism, recent cardiac surgery, and stroke. In addition, and reduces rate-related ischemia, thus, improving symptoms.
a review of possible iatrogenic causes including administration On the basis of parameters used in the AFFIRM trial, rate con-
of proarrhythmic medications like common sympathomimet- trol can be defined as having a resting heart rate of less than 80
ics should be made. Special attention to electrolyte abnormal- beats per minute and a maximal heart rate less than 110 beats
ities and correction should also be done. The ultimate goal per minute during a 6-minute walk [57]. AV nodal blocking
of therapy for otherwise hemodynamically stable patients who agents like beta-blockers and calcium channel blockers are the
develop acute onset AF is improvement of quality of life by con- most commonly used agents in this setting. These agents have
trolling rate, rhythm, or both, and providing anticoagulation predominantly safe profiles. Conversely, awareness of calcium
when indicated. channel blockers association with heart failure exacerbation
Strategies that focus on either rate control or rhythm control must be recognized in patients with low left ventricular ejec-
in hemodynamically stable patients may be used. Rate control tion fractions. Amiodarone may also be used to achieve rate
refers to an approach that uses AV nodal blocking agents to control. In patients with labile blood pressures, digoxin is of-
decrease ventricular rate and improve hemodynamics. Calcium ten used to provide rate control but may prove insufficient as
channel blockers, beta-blockers, or even AV nodal ablation may a single agent.
be used to control the ventricular rate. Conversely, rhythm con- Alternatively, in chronic settings beyond the scope of the
trol is an attempt to keep the patient in sinus rhythm. Strate- ICU, AV node ablation combined with permanent pacemaker
gies include cardioversion, antiarrhythmic drug treatment, per- implantation may be considered when pharmacologic rate con-
cutaneous ablation, and various surgical procedures. As dis- trol therapy is either unsuccessful or not tolerated [58,59]. It
cussed previously, the ultimate goal of treatment of AF is to is important to note that although AV node ablation decreases
improve the quality of life. Therefore, management with both symptoms and improves quality of life, studies have shown no
rate control and rhythm control provides the greatest improve- impact on overall survival [60,61].
ment in symptoms. However, the AFFIRM (Atrial Fibrillation
Follow-up Investigation of Rhythm Management) trial, a study Rate Control Issues in the Intensive Care Setting. Rate con-
of 4,060 patients older than 65 years with a history of AF and trol can be particularly difficult when patients are hypotensive
additional risk factors for stroke and death who were randomly in AF as a result of coexisting critical illness. Digitalization is
assigned to receive either rate control or rhythm control ther- sometimes effective; however, in states of high circulating cat-
apy showed no significant difference in improvement of qual- echolamines, digoxin is not useful. Administering intravenous
ity of life between rate control strategies and rhythm control calcium just prior to initiating an intravenous calcium chan-
strategies [56]. As a result, individualizing treatment strate- nel blocker (diltiazem, verapamil) may sometimes minimize
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450 Section III: Cardiovascular Problems and Coronary Care

hypotension while achieving reasonable rate control. Care- heart disease is present or not. In patients with structural heart
ful scrutiny of the utilization of intravenous sympathomimetic disease, intravenous amiodarone is preferred with attempt at
agents and titration of dose to decrease AV nodal conduction cardioversion either for hemodynamic instability or following
should be considered. For example, changing from high-dose initial amiodarone loading. In the absence of structural heart
dopamine or epinephrine to phenylephrine in a patient with disease, when oral medication can be administered, rate con-
septic shock may be sufficient to support the blood pressure trol with a beta-blocker and initiation of a class Ic agent is a
without necessarily increasing AV nodal conduction and thus common management strategy. In addition, the temporary use
rapid ventricular rates. of IV amiodarone can be considered until the medical illness
subsides and long-term rhythm control with less toxic antiar-
Rhythm Control rhythmic agents or with nonpharmacologic treatment options
can be considered [33,51,53,67,68].
Management of AF in stable patients may be geared toward
restoration of sinus rhythm. DC or chemical cardioversion
strategies can be employed. This may be a good option for
Prevention of Thromboembolic Complications
young patients, but older patients with cardiomegaly and left An important aspect in the management of AF is implemen-
atrial enlargement are less likely to have successful results. tation of risk-appropriate anticoagulation. Studies have con-
Hemodynamically stable patients who have documented de- sistently shown an increase in cardioembolic stroke rates in
velopment of acute AF for duration of 48 hours or less may patients with AF [6971]. In addition to causing a hyperco-
proceed with early cardioversion. Alternatively, hemodynami- agulable state, AF impairs proper atrial contraction leading
cally stable patients with AF that has lasted for more than 48 to blood stasis in the left atrium and ultimately a physiologic
hours or have an unknown duration of AF may still undergo state promoting thrombus formation [72,73]. Therefore, an
cardioversion. It is important to rule out intracardiac thrombus understanding of risk factors for stroke in patients with AF is
that may be associated with AF and can subsequently embolize essential. Risk factors may be easily remembered by using the
with cardioversion and return to normal sinus rhythm. There- mnemonic CHADS2, which stands for cardiac failure (recent
fore, two different strategies may be undertaken. First, trans- heart failure), history of hypertension, age greater or equal to
esophageal echocardiogram (TEE) can be utilized to rule out 75 years, history of diabetes, and a history of stroke or a tran-
intracardiac thrombus formation. Once thrombus is excluded sient ischemic attack [74]. The number 2 stands for the fact
by TEE, cardioversion may proceed using the aforementioned that a history of stroke counts as 2 risk factors points. The
strategies. Subsequent anticoagulation with warfarin is pru- CHADS2 mnemonic is also used as a risk stratifying score to
dent, with an INR goal of 2 to 3 for at least 4 weeks [62]. help predict patients at significantly increased risk of devel-
Another strategy that may be used in patients with AF that oping an ischemic stroke from a cardioembolic event in the
has lasted for more than 48 hours or unknown duration is to setting of AF [74]. Based on these scores, the annual predicted
anticoagulate with a goal INR of 2 to 3 for 3 weeks prior to stroke risk can be calculated. The adjusted annual stroke rate
cardioversion. Patients are subsequently instructed to continue increases from 1.9% in patients with a CHADS2 score of 0%
anticoagulation therapy for an additional 4 weeks after car- to 18.2% in patients with a CHADS2 score of 6.
dioversion to prevent thromboembolic events that may result Once the CHADS2 score and the risk for stroke are esti-
from delayed atrial mechanical recovery in this setting. mated for patients with AF, the decision on the type of prophy-
Concomitant use of antiarrhythmic medications with DC lactic antithrombotic therapy, if any, needs to be determined.
cardioversion increases the probability not only of success- On the basis of the 2006 ACC/AHA/ESC guidelines for the
ful cardioversion, but also maintenance of sinus rhythm for management of AF, aspirin 81 mg to 325 mg daily is recom-
longer periods of time. Because antiarrhythmic drugs have mended for patients with no risk factors for thromboembolism
many proarrhythmic side effects, the particular regimen chosen (CHADS2 score of 0) [75]. Patients with a single risk factor or
depends on the clinical setting and the underlying cardiovascu- a CHADS2 score of 1 may be managed with either aspirin 81
lar disease. Flecainide, propafenone, or sotalol are often used to 325 mg daily or an adjusted-dose warfarin regimen with an
for patients without underlying structural heart disease. Amio- INR goal of 2.0 to 3.0 [75]. For patients with risks that confer
darone and dofetilide are often recommended in patients with a high-risk score (a previous stroke or TIA, rheumatic mitral
underlying heart failure, while sotalol or dofetilide may be used stenosis, or a CHADS2 score of 2 or higher), warfarin is recom-
in patients with coronary artery disease. Consultation with a mended with an INR goal of 2.0 to 3.0 [75]. Anticoagulation
cardiologist is recommended. with other agents like unfractionated or low-molecular-weight
Drugs often used for chemical cardioversion in the acute set- heparin may be used as alternative bridging therapy in patients
ting include procainamide, flecainide, propafenone, dofetilide, requiring certain procedures or surgeries.
and ibutilide. Although this is often an appropriate strat-
egy, studies have shown pharmacologic cardioversion to be Anticoagulation Issues Relevant in the Intensive Care Unit.
less effective than DC cardioversion in combination with an- Appropriate anticoagulation in the critically ill patient is par-
tiarrhythmic drugs [63]. Studies have demonstrated a bet- ticularly problematic even when following present guidelines
ter outcome and safety profile with ibutilide compared with and using the CHADS2 scoring system [76,77]. Postsurgical
propafenone [64,65]. AV nodal blocking agents like beta- patients, patients at risk for intracranial bleeding, patients with
blockers or calcium channel blockers should be used with class closed head or closed chest trauma, etc., frequently have a con-
Ia and Ic antiarrhythmics to prevent conversion of AF to a slow traindication for systemic anticoagulation. If the patient has
atrial flutter with 1:1 AV conduction. chronic AF and the CHADS2 score is 2, in general, anticoag-
ulation can be safely discontinued for the period of the acute
Rhythm Control Issues in the Intensive Care Setting. A fre- illness. In patients with CHADS2 >2, anticoagulation free in-
quent clinical scenario in which AF is encountered in the ICU tervals should be minimized and aspirin provided if not also
is the postcardiac surgical patient. The incidence of AF in these contraindicated.
patients is high (8% to 34%) [33,49,66]. Because of this, un- For patients who are hemodynamically compromised with
less a contraindication is present, many ICUs use amiodarone new onset AF, urgent cardioversion can be performed regard-
prophylactically in the postoperative period. When AF occurs less of anticoagulation status. When less urgent, TEE may first
in other situations and rate control is suboptimal, the choice of be performed to exclude evidence of an intra-atrial thrombus
antiarrhythmic agent depends primarily on whether structural prior to cardioversion and reinitiation of anticoagulation when
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Chapter 42: Supraventricular Tachycardias: Recognition and Management in the Intensive Care Setting 451

the risk of bleeding is minimal [78,79]. Atrial appendage occlu- AV nodal blocking agents should be instituted simultaneously
sion devices, exclusion devices, or minimally invasive surgical when membrane active drugs, such as type Ic agents, are started
techniques may be particularly useful in these situations and for atrial flutter in the ICU setting.
are being investigated for clinical efficacy and safety [80,81]. Patients with persistent atrial flutter, especially of more than
a years duration may have significant underlying sinus node
dysfunction. When cardioversion or pace termination of the
Atrial Flutter flutter is planned, prolonged sinus node pauses may occur, and
standby external or endocardial temporary pacing should be
Atrial flutter, like AF, is one of the most common arrhythmias considered [87] (Fig. 42.11).
encountered in the critically ill patient. It is identified by a
characteristic sawtooth pattern of atrial activity at an atrial
rate of 240 to 320 beats per minute. Although variable ven- Multifocal Atrial Tachycardia
tricular conduction may occur, a 2:1 transmission commonly
transpires, resulting in a ventricular response rate of about 150 Another commonly encountered irregular narrow complex
beats per minute. The mechanism of common atrial flutter is tachycardia in the ICU is multifocal atrial tachycardia (MAT).
a macroreentry loop around the tricuspid annulus. The loop This SVT is caused by several abnormal atrial foci. Thus, MAT
often runs in a counterclockwise direction, causing negative is characterized by at least three different P wave morphologies
flutter waves in the inferior leads (II, III, aVF). Other reentry in a single lead with variable PR intervals. The atrial rate often
patterns may also be encountered but are beyond the scope of varies between 100 and 180 beats per minute with no single,
this chapter. Occasionally the ventricular rate may be greater dominant pacemaker. MAT is highly associated with underly-
than 150 beats per minute, making identification of the flutter ing pathologic processes that increase atrial pressures. Com-
waves difficult. Vagal maneuvers like carotid sinus massage or mon etiologies for the development of MAT include chronic
adenosine, a medication that briefly blocks AV nodal conduc- obstructive pulmonary disease, pneumonia, pulmonary em-
tion, may be used in these instances to slow down the rate and bolism, mitral stenosis, and congestive heart failure. Other
allow for more accurate identification of the arrhythmia. common causes include various electrolyte and acidbase dis-
Patients with an acute onset of atrial flutter often present turbances. Management of MAT involves aggressive treatment
with symptoms of palpitations, dyspnea, chest discomfort, and of the underlying disease. Acute measures aimed at ventricular
worsening symptoms of heart failure. As with AF, prompt as- rate control include calcium channel blockers or beta-blockers
sessment of hemodynamic status is critical in this setting. Man- with varying degrees of success [8890]. It is important to note
agement of atrial flutter is similar to AF, and the same guidelines that because this particular population is more prone to bron-
for rate control, rhythm control, and anticoagulation apply chospastic disease, calcium channel blockers may be preferred.
[82]. Rate control in atrial flutter often proves more difficult Digoxin should not be used in this setting, as it shortens atrial
than in AF. Unlike AF, which has multiple reentrant wavelets, refractoriness which may worsen the rhythm.
typical atrial flutter is composed of a single, fixed reentrant
pathway that provides a target amenable to cure by radiofre-
quency catheter ablation. Ablation is usually performed within Multifocal Atrial Tachycardia in the
the right atrium between the tricuspid annulus and the inferior Intensive Care Setting
vena cava to interrupt the atrial flutter circuit [83]. Atrial flutter Rate control can be extremely difficult with this arrhythmia.
not associated with a typical reentrant circuit has less successful Unless underlying theophylline toxicity or hypoxia is corrected,
ablation outcomes [84]. Ablation of the AV node with subse- managing rapid ventricular rates and symptoms resulting from
quent permanent pacemaker implantation, a method used in deleterious hemodynamic effects are often futile. Consideration
management of AF, may be an option in certain circumstances. for AV node ablation in refractory patients even in the setting
of critical illness can be considered, especially if rapid rates
Managing Atrial Flutter in the Intensive Care Unit compromise attempts to manage the patients hypotension and
other complicating medical illnesses. Intravenous magnesium
Atrial flutter is frequently an unstable arrhythmia in terms of
as hypoxia is being addressed may also help temporize patient
ventricular rate response. Specific caution is necessary when
compromise until hypoxia is corrected or a definitive procedure
instituting -adrenergic agents in patients with otherwise well-
is performed [91].
controlled response rates. Rapid change from 2:1, 3:1 AV con-
duction to 1:1 conduction and ventricular rates of 300 beats per
minute or more can occur. Such abrupt changes in ventricular
rate are uncommon with AF but should be expected with atrial SUMMARY
flutter. Cardioversion to sinus rhythm prior to initiating phar-
macological agents that enhance AV nodal conduction should Management of SVT in critically ill patients can be challenging.
be considered. Unlike with AF, immediate recurrence of atrial To maximize results, quick and accurate diagnosis of the exact
flutter is uncommon, and therefore, routine administration of arrhythmia mechanism is required. The caregiver should have
an antiarrhythmic agent to prevent return may not be required. an approach to analyzing the electrocardiogram during SVT. If
Urgent radiofrequency ablation for atrial arrhythmia is rare a regular narrow complex tachycardia is noted, then a careful
in the critically ill patient. However, if atrial flutter with rapid search for the P wave should be made. An abrupt onset arrhyth-
rates and recurrence following cardioversion is seen, the pro- mia with a short RP interval is likely a reentrant SVT either
cedure can be considered. Procedural success for atrial flutter AVNRT or AVRT. In both arrhythmias, adenosine for imme-
ablation is highest for cavotricuspid isthmus dependent flutter. diate conversion of the arrhythmia and intravenous AV nodal
This specific arrhythmia can be recognized by the flutter wave blocking therapy for prevention of recurrence is highly effec-
morphology wherein the terminal segment of the flutter wave tive. Cardioversion is of little value in this situation because of
in lead V1 is positive [85,86]. The use of antiarrhythmic agents the likelihood of recurrence and the almost certain conversion
like procainamide or flecainide may further organize an atrial of the arrhythmia with pharmacological agents. When the P
flutter and decrease the atrial rate of the flutter. This may, how- wave is difficult to identify, examine the terminal portion of
ever, paradoxically result in more rapid ventricular conduction the QRS complex to look for pseudo R waves (lead V1 ) or
which can be consequential in critically ill patients. Low dose pseudo S waves (leads II, III, and aVF) (Fig. 42.12).
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452 Section III: Cardiovascular Problems and Coronary Care

FIGURE 42.11. Slow supraventricular tachyarrhythmia. In a critically ill patient, the initial arrhythmia
may be mistaken for sinus tachycardia. However, closer scrutiny of the P wave morphology defines a
non-sinus mechanism (absence of terminal negative portion in the P wave in lead V1 ). Note the abrupt
termination that would essentially exclude a sinus mechanism. If recurrences are seen and associated with
hemodynamic changes, intravenous antiarrhythmic agents can be considered. Automatic atrial tachycar-
dias are often catecholamine sensitive, and when possible, the use of these agents for therapy should be
minimized when the arrhythmia is seen. Note also the significant pause on termination of the arrhythmia
suggesting underlying sinus node dysfunction.

FIGURE 42.12. 12-Lead electrocardiogram in a patient with symptomatic atrioventricular node reen-
try during hospitalization. Note the P waves are difficult to define; however, the late S waves easily
recognized in leads II, III, and aVF (pseudo S wave) are characteristic of this arrhythmia.
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Chapter 42: Supraventricular Tachycardias: Recognition and Management in the Intensive Care Setting 453

TA B L E 4 2 . 1
SUMMARY OF EVIDENCE-BASED RECOMMENDATIONS FOR TREATMENT OF VARIOUS SUPRAVENTRICULAR
TACHYCARDIAS

Disease Treatment

Atrioventricular nodal reentrant tachycardia (AVNRT) Adenosine


Calcium channel blockers
Beta-blockers
Atrioventricular reentry tachycardia (AVRT) Adenosine
hemodynamically stable Calcium channel blockers
Beta-blockers
Procainamide
Refer for possible ablation therapy
AVRT with underlying atrial fibrillation/atrial flutter AV node blocking agents contraindicated
AVRT with wide complex (WPW)hemodynamically unstable Urgent cardioversion
AVRT with wide complex (WPW)hemodynamically stable Procainamide
Atrial fibrillation See text regarding anticoagulation
Hemodynamically stable Rate control: Beta-blockers, calcium channel blockers,
amiodarone, digoxin, AV junction ablation
Rhythm control: Cardioversion, antiarrhythmic drug
treatment, ablation, various surgical procedures
Hemodynamically unstable DC cardioversion
Procainamide or ibutilide may be used in cases of wide-complex
tachycardia (underlying WPW)
Atrial flutter Management approach similar to atrial fibrillation
Multifocal atrial tachycardia Calcium channel blockers
Beta-blockers

Note: Identifying an underlying cause of arrhythmia should always be attempted.

For a gradual onset tachycardia with a long RP interval, If an irregular SVT is noted, AF is most likely, but a search
either sinus tachycardia, inappropriate sinus tachycardia, or for regular flutter waves or multiple P wave morphologies (mul-
atrial tachycardia is likely. If the P wave morphology is not con- tifocal atrial tachycardia) is needed since these latter arrhyth-
sistent with sinus rhythm, then an atrial tachycardia is present, mias require a different management approach as detailed in
and antiarrhythmic therapy with rate control is likely effec- the text.
tive. If the P wave morphology is consistent with sinus rhythm, Atrial fibrillation is by far the most common SVT arrhyth-
sinus tachycardia is most likely, and treatment directed to the mia encountered in the critical care setting. For each patient,
underlying mechanism (blood loss, fever, hypotension, etc.) will rate control should be optimized, anticoagulation issues ad-
likely result in eventual decrease in the sinus rates. No specific dressed, and when symptoms continue despite these measures,
rhythm-based therapy is required. Inappropriate sinus tachy- restoration of sinus rhythm strongly considered.
cardia should be considered when no underlying cause for rapid A summary of evidence-based management of supraventric-
sinus rates is noted and is often seen in the critically ill patient ular tachycardia is given in Table 42.1.
following the period of stress.

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CHAPTER 43 BRADYARRHYTHMIAS AND


TEMPORARY PACING
GAURAV A. UPADHYAY AND JAGMEET P. SINGH

can occur in the setting of myocardial ischemia, drug toxic-


INTRODUCTION ity or overdose, and severe electrolyte disturbance. Manage-
ment begins by identifying the etiology of bradyarrhythmia
Implicated in over 40% of sudden cardiac deaths in the hos- and then attempting to restore normal sinus rhythm by cor-
pital, bradyarrhythmias are an important and heterogeneous rection or elimination of the identified precipitant. In situa-
group of cardiac rhythm disturbances [1]. Broadly classified, tions where the bradyarrhythmia causes acute hemodynamic
bradyarrhythmias are the manifestations of either a failure of instability, the need for either pharmacologic intervention or
cardiac impulse generation or impulse conduction leading to electrical support through temporary cardiac pacing must be
heart rates slower than normal sinus rhythm. By historical evaluated.
convention, normal sinus rhythm is defined between 60 and The purpose of this chapter is to review the pathophysi-
100 beats per minute. Normal sinus rhythm is spontaneously ology of various bradyarrhythmias and to review treatment
generated by depolarizing pacemaker cells in the high right options available. Particular attention is placed on transcuta-
atrium within the sinoatrial (SA) node, and conducted through neous and transvenous pacing, as these advanced modalities
the atrium across internodal pathways to the atrioventricular are commonly employed in the medical and cardiac intensive
(AV) node and subsequently to the bundle of His and to the care settings.
left and right bundle branches of the Purkinje system [2,3].
Bradyarrhythmias may either be physiologic and benign, as in
sinus bradycardia in athletes, or pathologic and warranting in-
tervention, as in symptomatic bradycardia from either sinus
PATHOPHYSIOLOGY
node dysfunction or ventricular asystole from high-grade AV
block. Disorders of Impulse Generation
Bradyarrhythmias may arise through several distinct mech-
anisms. Reduced automaticity in the SA node may be driven The most commonly encountered bradyarrhythmias of the nor-
by hypoxia, hypothermia, or increased parasympathetic influ- mal conduction system include sinus bradycardia and sinus
ence from gastrointestinal distress or genitourinary dysfunc- arrhythmia, both of which can be manifestations of normal
tion. Periatrioventricular inflammation may reduce impulse physiologic states. Arbitrarily defined as a sinus node impulse
propagation, as in Lymes disease, myocarditis, or systemic rate of less than 60 beats per minute, sinus bradycardia may
lupus erythematosus. Significant AV and even infranodal block be a manifestation of an enhanced vagal tone seen commonly
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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456 Section III: Cardiovascular Problems and Coronary Care

in athletes. Increased parasympathetic and decreased sympa- TA B L E 4 3 . 1


thetic tone during sleep also leads to bradycardic resting heart
rates in nonathletes. Sinus arrhythmia is characterized as pha- CARDIOACTIVE DRUGS THAT MAY INDUCE OR
sic changes observed in heart rate, secondary to autonomic WORSEN SINUS NODE DYSFUNCTION
influences on the sinus node triggered by normal respiration.
Beta-blockers
Sinus Arrhythmia Calcium channel blockers (e.g., verapamil, diltiazem)
Sympatholytic antihypertensives (e.g., -methyldopa,
Thought to be due to reflex inhibition of vagal nerve tone dur- clonidine, guanabenz, reserpine)
ing inspiration, sinus arrhythmia is the reduction in time from Cimetidine
one P wave to another (P-P interval) between sinus discharges, Lithium
leading to an increase in heart rate during inspiration and slow- Phenothiazines (rarely)
ing during expiration, which is thought to help improve and Antihistamines
synchronize alveolar gas exchange [4]. As such, respiratory si- Antidepressants
nus arrhythmia is considered the sign of a healthy conduction Antiarrhythmic agents
system. Marked sinus arrhythmia may even manifest with sinus May cause sinus node dysfunction (SND) in normal subjects:
pauses for 2 seconds or longer, but is rarely pathologic by it- amiodarone
self. Small changes in P-wave morphology and PR interval can Frequently worsens mild SND: flecainide, propafenone,
be attributed to variation in the pacemaking site within the SA sotalol
node due to differential vagal stimulation. This periodicity in Infrequently worsens mild SND: digitalis, quinidine,
the heart rate is most pronounced in the young and decreases procainamide, disopyramide, moricizine
with age. The direct impact of the autonomic nervous system on Rarely worsens mild SND: lidocaine, phenytoin, mexiletine,
the sinus node and sinus arrhythmia is confirmed by the fact tocainide
vagal tone can be abolished through parasympathetic block- Opioid blockers
ade by atropine or through anatomic denervation of hearts
after cardiac transplant. Autonomic system dysregulation due Adapted from Podrid, Kowey: Cardiac Arrhythmia. Philadelphia, PA,
to microvascular disease (as in diabetes) or degeneration (as Lippincott Williams and Wilkins, 2001 (Permission needed).
in ShyDrager syndrome) also reduces sinus arrhythmia. In-
deed, depression of respiratory sinus arrhythmia after myocar-
dial infarction is associated with an increased risk of sudden
cardiac death [5]. In contrast to respiratory sinus arrhythmia,
mias and tachyarrhythmias. These may originate in the atrium
nonrespiratory sinus arrhythmia is the change of P-P intervals
(e.g., atrial tachycardias, multifocal atrial rhythms, paroxysmal
varying at random and may reflect drug toxicity from digitalis,
atrial fibrillation) or ventricles (e.g., idioventricular rhythms,
intracranial hemorrhage, or ischemic heart disease [6].
ventricular tachycardias [VTs]). Coexisting AV nodal distur-
bance and block are also common, and intermittent periods of
Sinus Bradycardia bradycardia punctuated by tachycardia have given rise to the
Symptomatic sinus bradycardia or sinus pauses causing re- term tachybrady syndrome. Many of these patients go on
duced cardiac output or hemodynamic instability may be to need permanent pacemakers for effective rate control. The
due to extracardiac disorders which profoundly increase va- presentation in the intensive care setting is often due to an ex-
gal tone such as bowel obstruction, urinary retention, nau- acerbation of the underlying sinus node dysfunction through
sea and vomiting, or intracranial mass. Pharmacologic agents the use of cardioactive medications (see Table 43.1), which may
such as parasympathomimetic drugs, digitalis, beta-adrenergic- result in a reduced cardiac output from diminished heart rate
blocking drugs, and calcium antagonists can also exacerbate or unstable tachyarrhythmias. Given the diversity of potential
sinus bradycardia. Other disorders, such as carotid sinus hy- etiologies and manifestations of sinus node dysfunction, it is
persensitivity may also increase vagal tone and lead to tran- often more useful to distinguish temporary or reversible causes
sient ventricular asystole due to sinus arrest lasting up to 3 of the syndrome (e.g., drug toxicity) from permanent etiologies
seconds or longer. Although some patients may require perma- (e.g., idiopathic fibrosis, degenerative changes of the conduc-
nent pacemaker implantation due to recurrent, activity-related tive system) to identify the appropriate management strategy.
symptomatic pauses, they rarely require temporary pacemaker
support as the negative chronotropic effect is relieved once
pressure is removed from the carotid.
Disorders of Impulse Conduction
Sinus Node Dysfunction
Conduction block may occur at any point in the conduction
Inappropriate SA node automaticity and disordered impulse system and represents a failure of impulse propagation. This
generation is called sinus node dysfunction (also described as can occur at the level of the SA node, as in SA exit block, or
sick sinus syndrome by Ferrer [7]). It is commonly a disorder of further downstream, as in AV block or interventricular block.
senescence, although can occur at any age due to destruction of Importantly, conduction block is distinct from the normal phys-
sinus node cells through infiltration, collagen vascular disease, iologic phenomenon of interference, in which a preceding im-
trauma, ischemia, infection, or idiopathic degeneration [8]. Si- pulse causes a period of refractoriness due to inactivation of
nus node dysfunction affects men and women equally, com- ion channels. Common terminology also differentiates between
monly in the age range of 65 to 75 years, and is the primary in- first-degree block, in which an impulse is delayed; second-
dication for over 50% of permanent pacemaker implants in the degree block, in which impulses are intermittently transmitted;
United States [9,10]. Indeed, sinus node dysfunction comprises and third-degree block, in which impulses are not transmitted
of a constellation of abnormalities of the sinus node charac- and dissociation may ensue. Bradyarrhythmias usually result
terized by inappropriate sinus bradycardia (in the absence of from a combination of conduction block and disordered au-
drugs), sinus arrest and chronotropic incompetence. Subsidiary tomaticity, for example, as in sinus rhythm with third-degree
and latent pacemakers further downstream become active in heart block and bradycardic junctional escape rhythm. Com-
states of such dysfunction, and can give rise to bradyarrhyth- mon types of conduction block are briefly reviewed here.
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Chapter 43: Bradyarrhythmias and Temporary Pacing 457

Sinoatrial Block tion of an atrial impulse without change in preceding PR in-


terval. Attention should be taken to distinguish Mobitz type-II
SA block, also called SA exit block, manifests as sinus arrest
block from block of a premature atrial complex, which is due to
of variable length on the surface ECG. On the basis of a study
physiologic interference and not due to pathological involve-
of U.S. Air Force personnel, the prevalence is approximately
ment of the AV node. Mobitz type-II block is of significance
1% in otherwise normal subjects [11]. Considered by some
in the clinical setting, as it may herald impending complete
to be a manifestation of sinus node dysfunction, the patho-
heart block, particularly when multiple consecutive impulses
physiology of SA block is a defect of impulse generation or
are nonconducted (often referred to as advanced or high-
propagation within the SA node. First-degree SA block cannot
grade heart block). Third-degree AV block, or complete heart
be detected on surface ECG as sinus node depolarization is not
block, occurs with the absence of atrial impulse propagation
inscribed separately from atrial depolarization (the P wave).
to the ventricles and will manifest with ventricular standstill in
Type I second-degree SA block is the progressive prolongation
the absence of an escape rhythm. When reversible etiologies are
of conduction block within the sinus node until complete exit
present, temporary pacing is critical toward providing electri-
block occurs. This manifests on surface ECG as progressive
cal support, especially in the setting of ventricular asystole due
shortening of P-P intervals till a pause occurs. Type II second-
to complete heart block. Temporary pacing is indicated when
degree SA block is the spontaneous block of a sinus impulse
the subsidiary escape rhythm is unstable and cannot maintain
which leads to a sinus pause whose duration is an exact multi-
hemodynamic stability, leading to cerebral hypoperfusion or
ple of the preceding P-P interval. Third-degree SA block simply
further cardiac instability
manifests as sinus arrest, usually with the eventual appearance
Similar to sinus node dysfunction, there are myriad etiolo-
of a subsidiary pacemaker rhythm such as a junctional escape.
gies which may lead to AV block. In the intensive care setting,
Sinus node dysfunction can be studied in the electrophysiology
common etiologies include electrolyte disturbance, notably
laboratory and quantified by techniques to specifically examine
hyperkalemia or hypermagnesemia; drug toxicity, particularly
the sinus node electrograms, sinus node recovery time, and SA
from cardioactive drugs such as beta-adrenergic-blocking
conduction studies. In the intensive care setting, diagnosis can
agents, nondihydropyridine calcium-channel blockers, digi-
be challenging, and it is usually sufficient to simply be able to
talis derivatives, and antiarrhythmics; myocardial ischemia
recognize third-degree SA block which may necessitate tempo-
from inferior or anteroseptal infarction; infection from
rary pacing if subsidiary pacemakers are not active or do not
myocarditis or endocarditis, particularly involving the aortic
provide sufficient cardiac output.
valve; and trauma from cardiac surgery, catheter trauma, or
radiation. Clinical history obtained from the patient is critical
Atrioventricular Block in determining the potential duration of the block and also
AV block is frequently observed on surface electrocardiogra- prioritizing appropriate treatment modalities.
phy, and may anatomically occur anywhere in the conduction
system outside of the SA node. It is clinically important to at-
tempt to distinguish AV block at the level of the AV node with
Intraventricular Block
block within or below the level of the His bundle, as infranodal Failure in ventricular activation due to block in the His
block may be associated with instability and a worse clinical Purkinje system may also be the cause of complete heart block.
outcome. First-degree AV block is defined as a prolongation The left and right bundle branches are commonly divided into
of the PR interval greater than 0.20 seconds, and is generally a trifascicular system, consisting of the right bundle branch and
felt to be due to a block of impulse conduction at the level of the left anterior and posterior fascicles [17]. Although a sep-
the AV node, although when associated with bundle-branch tal fascicle has also been identified in anatomic studies, ECG
block, may occur further down in the HisPurkinje system. manifestations of septal conduction block are debated and re-
In a study of over one hundred thousand airmen, the preva- main to be defined [18]. Bifascicular block is present when
lence of first-degree AV block was found to be 0.65% [12]. In either left anterior or left posterior fascicular block is associ-
a 30-year longitudinal study, the association of first-degree AV ated with right bundle branch block. Clinically, complete heart
block with a narrow QRS complex was thought to be largely block is most often preceded by chronic bifascicular block, al-
benign [13]. More recent data from the Framingham cohort, though the progression is often slow [19]. However, when first-
however, suggest that significant PR prolongation may be as- degree AV block is associated with chronic bifascicular block
sociated with increased risks of atrial fibrillation, pacemaker and symptomatic bradycardia, there is an increased risk of sud-
implantation, and all-cause mortality over time [14]. Marked den cardiac death (this combination is sometimes erroneously
first-degree AV block may lead to hemodynamic derangement referred to as trifascicular block). Alternating bundle branch
when atrial systole occurs in close proximity to the preceding block seen on successive ECG tracings, either manifesting with
ventricular systole, manifesting with symptoms similar to the sequential right and left bundle branch block, or right bun-
pacemaker syndrome, although this is rare [15]. In the intensive dle branch block with left anterior and left posterior fascicu-
care setting, second- and third-degree AV block are of greater lar block, is also associated with increased mortality and can
significance. be correctly identified as representing intermittent trifascicular
Second-degree AV block was classified into two types by block.
Mobitz in 1924 [16]. Mobtiz type-I second-degree AV block, Similar to other forms of conduction block, there are nu-
or Wenckebach-type block, is characterized by progressive pro- merous potential etiologies which may lead to intraventricular
longation of the PR interval before nonconduction. Analogous block, although ischemia in the setting of a myocardial infarc-
to type I SA block which demonstrates shortening of P-P inter- tion (MI) is the most common in the intensive care setting.
vals, there is progressive shortening of the R-R intervals prior The SA nodal artery receives its blood supply from the prox-
to a dropped beat in Mobitz type-I block. Irrespective of QRS imal right coronary artery in 55% of the population, from
width, Mobitz type-I block, or Wenckebach phenomenon, usu- the circumflex in 35%, and from both in approximately 10%.
ally represents an appropriate physiologic response to increas- The AV nodal artery, on the other hand, arises from the poste-
ing heart rate through decremental conduction in the AV node, rior descending artery in 80% of cases, 10% from the circum-
and rarely requires intervention. Mobitz type-II block, on the flex, and approximately 10% from both arteries. Although,
other hand, usually represents infranodal disease, particularly an inferior MI may lead to varying degrees of AV block from
when associated with a wide complex QRS. On the surface AV nodal artery ischemia or enhanced vagal tone from exag-
ECG, Mobitz type-II block manifests as a sudden nonconduc- geration of the BezoldJarisch reflex, intraventricular block is
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458 Section III: Cardiovascular Problems and Coronary Care

uncommon. An anterior MI, on the other hand, may cause is- score (number of characteristics on presenting ECG) and the
chemia of the fascicles directly and is associated with greater development of complete heart block. Patients without ECG
extent of left ventricular dysfunction. In the prethrombolytic evidence of any conduction block on presentation had a less
era, new fascicular or bundle branch blocks were common af- than 4% risk of subsequent complete heart block, in contrast
ter an MI and were associated with a significantly increased to those with scores of two, in whom the risk of developing
risk of mortality [20]. A simple scoring model characteriz- complete heart block was 45%. Because of the relatively com-
ing the risk of progression to complete heart block after MI mon incidence of bradycardia after MI, the American Col-
was developed by Lamas based on ECG criteria [21]. Patients lege of Cardiology (ACC) and the American Heart Associa-
with evidence of conduction block on ECG, including first or tion (AHA) have clear guidelines on intervention, including
second-degree block (both type I and type II), left anterior and the use of temporary pacing, for AV and intraventricular dis-
posterior fascicular block, right bundle branch block, or left turbance (Table 43.2), which will also be further discussed
bundle branch block had a linear relationship between their later.

TA B L E 4 3 . 2
ACC/AHA GUIDELINES FOR TREATMENT OF ATRIOVENTRICULAR AND INTRAVENTRICULAR CONDUCTION
DISTURBANCES DURING STEMIa

Application of transcutaneous patches and standby transcutaneous pacing


Class I
Normal AV conduction or first-degree AV block or Mobitz type-I second-degree AV block with new bundle branch block
Normal AV conduction or first-degree AV block or Mobitz type-I second-degree AV block with fascicular block + RBBB
First-degree AV block with old or new fascicular block (LAFB or LPFB) in anterior MI only
First-degree AV block or Mobitz type-I or type-II second-degree AV block with old bundle branch black
Mobitz type-I or type-II second-degree AV block with normal intraventricular conduction
Mobitz type-I or type-II second-degree AV block with old or new fascicular block (LAFB or LPFB)
Class IIa
First-degree AV block with old or new fascicular block (LAFB or LPFB) in nonanterior MI only
Class IIb
Alternating left and right bundle branch block
Normal AV conduction with old bundle branch block
Normal AV conduction with new fascicular block (LAFB or LPFB)
First-degree AV block with normal intraventricular conduction
Mobitz type-II second-degree AV block with new bundle branch block
Mobitz type-II second-degree AV block with fascicular block + RBBB
Class III
Normal AV conduction with normal intraventricular conduction
Temporary transvenous pacing
Class I
Alternating left and right bundle branch block
Mobitz type-II second-degree AV block with new bundle branch block
Mobitz type-II second-degree AV block with fascicular block + RBBB
Class IIa
First-degree AV block or Mobitz type-I second-degree AV block with new bundle branch block
First-degree AV block or Mobitz type-I second-degree AV block with fascicular block + RBBB
Mobitz type-II second-degree AV block with old bundle branch block
Mobitz type-II second-degree AV block with normal intraventricular conduction
Mobitz type-II second-degree AV block with old or new fascicular block (LAFB or LPFB) in anterior MI only
Class IIb
Normal AV conduction with new bundle branch block
Normal AV conduction with fascicular block + RBBB
Mobitz type-I or type-II second-degree AV block with old bundle branch block
Mobitz type II second-degree AV block with old or new fascicular block (LAFB or LPFB) in nonanterior MI only
Class III
Normal AV conduction or first-degree AV block or Mobitz type-I second-degree AV block with normal intraventricular conduction
Normal AV conduction or first-degree AV block or Mobitz type-I second-degree AV block with old or new fascicular block (LAFB or
LPFB)
Normal AV conduction with old bundle branch block
a
Except where specified, all indications include anterior and nonanterior MI.
AV, atrioventricular; BBB, bundle branch block; BP, blood pressure; LAFB, left anterior fascicular block; LBBB, left bundle branch block; LPFB, left
posterior fascicular block; MI, myocardial infarction; RBBB, right bundle branch block.
Adapted from the 2004 ACC/AHA Guidelines for the management of patients with ST-elevation myocardial infarction. Circulation 110:e82e293, 2004
(Permission needed).
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Chapter 43: Bradyarrhythmias and Temporary Pacing 459

loop diuretic, sodium polystyrene sulfonate). These types of


TREATMENT medical interventions must be tailored with attention to the
underlying etiology of the bradyarrhythmia, along with con-
Appropriate management of bradyarrhythmia is predicated current assessment of whether advanced support through tem-
upon identification of potential etiologies, selection of appro- porary cardiac pacing is indicated.
priate medical therapy, and assessment requirement for tempo-
rary cardiac pacing to maintain hemodynamic stability. Given
the heterogeneous causes for bradyarrhythmias, in the acute Device Therapy
setting it is critical to (1) identify and correct potential precip-
itants, (2) define a period for which medical or device therapy Temporary cardiac pacing involves the application of electrical
will be tried in the short term, and (3) identify the need for stimulation to the heart in order to override intrinsic rhythm
permanent pacing if it exists. and provide an exogenous source of pacemaking function.
Whereas guidelines for permanent pacing have been clearly
summarized by the ACC, the AHA, and the Heart Rhythm
Medical Therapy Society (see Table 43.3), indications for temporary cardiac
pacing outside of acute MI remain undefined and up to in-
Upon initial presentation to the hospital emergency depart- dividual clinical assessment [32]. The most frequent use of
ment, compromising bradycardia (or bradyarrhythmia leading temporary cardiac pacing is to improve circulatory hemody-
to hemodynamic insufficiency) may be successfully resolved by namics by improving cardiac output through increased heart
conservative measures such as making the patient lie flat and rate in the setting of symptomatic bradycardia (i.e., bradycar-
bed rest in up to 40% of patients. Approximately 60%, how- dia resulting in hypotension, cerebral hypoperfusion, or result-
ever, require some form of pharmacologic therapy and 20% ing systemic effects). Overdrive pacing of the heart may also
of these will go on to require advanced intervention with tem- be used to terminate some types of tachyarrhythmias, includ-
porary pacing [22]. Conservative medical therapy is an effec- ing sinus node reentry, AV node reentry, and AV reciprocating
tive measure for treating symptomatic bradycardia when ap- tachycardia with accessory bypass tract, although is rarely used
plied with attention to potential etiology. Atropine (0.6 to 1.0 for this purpose in clinical practice given the efficacy of med-
mg IV repeated every 5 minutes until desired effect or max- ications and cardioversion [33]. There is still a role, however,
imum dose of 0.04 mg per kg), is an anticholinergic whose for suppression of pause-dependent polymorphic VT (torsades
well-documented vagolytic properties lead to increase in heart de pointes) in limited situations while concurrent treatment of
rate as well as blood pressure in settings of enhanced parasym- the underlying metabolic disturbance or proarrhythmic trigger
pathetic tone [23]. It has also been studied extensively in the is underway [34].
setting of MI, and although may be associated with a small risk The decision to employ temporary cardiac pacing is made
of worsening ischemia, is the drug of choice for treatment of AV with attention to the temporality of the inciting arrhythmia. If
block after inferior MI [24,25]. However, care should be taken the bradyarrhythmia is thought to be due to a transient precip-
to begin with doses of 0.6 mg or greater, as lower doses may itant which can be managed pharmacologically (as described
cause a paradoxical increase in bradycardia. Aminophylline in- earlier), medications are generally preferred due to their lower
fusion (50 to 250 mg administered over 60 seconds, repeating infectious and mechanical complication rates. Nearly 50% of
as necessary) has also been studied in atropine-resistant AV patients in whom temporary pacing is used, however, ulti-
block after inferior myocardial infarction [26]. Aminophylline mately require permanent pacemakers before discharge (see
has been shown to be effective in humans, and its mechanism of also Table 43.3) [35]. In these patients, delay in use of tem-
action is via the antagonism of locally accumulating adenosine porary pacing may expose patients to adverse outcomes.
during ischemia [27,28]. According to the 2005 AHA Guide- Modalities which are available to deliver electrical stimula-
lines regarding cardiopulmonary resuscitation, epinephrine (1 tion include transcutaneous patches, transvenous endocardial
to 2 mg IV bolus along with 2 to 10 g per min infusion) leads, epicardial leads (usually placed at the time of surgery),
may also be considered for symptomatic bradycardias that are transthoracic pacing through percutaneous needle insertion
nonresponsive to atropine [29]. through the chest wall, or pacing through esophageal elec-
Isoproterenol infusions (5 to 20 g per minute) or dopamine trodes (which is primarily used for atrial pacing). Cardiac stim-
(5 to 20 g per kg per minute) may also be used in an attempt to ulation has also been demonstrated in humans through tran-
stimulate chronotropy during nonischemic bradyarrhythmias. scutaneous ultrasound energy delivery, although this approach
These infusions should particularly be used cautiously in the remains largely investigational [36]. Although epicardial lead
setting of cardiogenic shock since they reduce coronary perfu- placement is common after cardiac surgery, the most commonly
sion pressure and substantially increase the risk of worsening used modalities in medical and intensive care units are transcu-
myocardial ischemia. Pharmacologic overdose is a common eti- taneous and transvenous pacing.
ology of bradyarrhythmia. Glucagon (initial dose of 0.05 mg
per kg or 3 to 5 mg followed by continuous infusion of 1 to
Transcutaneous Pacing
5 mg per hour) may also be of significant benefit in bradycardias Temporary pacing has been used for the management of
due to beta-adrenergic or calcium antagonist toxicity [30]. By bradyarrhythmias since 1952, when the technique of tran-
activating adenyl cyclase, glucagon increases cyclic AMP and scutaneous pacing was initially described by Paul Zoll, who
increases intracellular calcium ion flux independently from the delivered a pulsating current through two electrodes attached
adrenergic receptor [31]. via hypodermic needles to the chest walls of two patients with
Other common causes of bradyarrhythmia include elec- ventricular standstill [37]. Since that time, transcutaneous pac-
trolyte disturbance and acidosis. When bradycardia is thought ing has emerged as the first-line nonpharmacologic therapy for
to be driven by acidosis, temporizing measures may include symptomatic bradycardia. Transcutaneous pacing systems con-
administration of sodium bicarbonate (1 mEq per kg) prior to sist of a pulse generator attached to high impedance external
initiation of hemodialysis or continuous venovenous hemofil- patch electrode pads (see Fig. 43.1). Most newer systems also
tration. Similarly, the treatment of hyperkalemia often involves incorporate defibrillator function in a stand-alone unit that
immediate steps to shift potassium to the intracellular com- provides combined antibradycardia, antitachycardia, and de-
partment (e.g., calcium, glucose, insulin), along with initiation fibrillation capacity [38]. Pacing parameters have not changed
of longer-acting agents to stimulate potassium excretion (e.g., over the past three decades, and include output, sensitivity, and
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460 Section III: Cardiovascular Problems and Coronary Care

TA B L E 4 3 . 3
ACC/AHA/HRS CLASS I RECOMMENDATIONS FOR PERMANENT PACING

Recommendations for permanent pacing in sinus node dysfunction


SND with documented symptomatic bradycardia, including frequent sinus pauses that produce symptoms
Symptomatic chronotropic incompetence
Symptomatic sinus bradycardia that results from required drug therapy for medical conditions
Recommendations for permanent pacing in acquired atrioventricular block in adults
Third-degree and advanced second-degree AV block at any anatomic level associated with bradycardia and symptoms (including
heart failure) or ventricular arrhythmias presumed to be due to AV block
Third-degree and advanced second-degree AV block at any anatomic level associated with arrhythmias and other medical conditions
that require drug therapy that results in symptomatic bradycardia
Third-degree and advanced second-degree AV block at any anatomic level in awake, symptom-free patients in sinus rhythm, with
documented periods of asystole 3.0 sec or any escape rate less than 40 bpm, or with an escape rhythm that is below the AV node
Third-degree and advanced second-degree AV block at any anatomic level in awake, symptom-free patients with AF and
bradycardia with 1 or more pauses of at least 5 sec or longer
Third-degree and advanced second-degree AV block at any anatomic level after catheter ablation of the AV junction
Third-degree and advanced second-degree AV block at any anatomic level with postoperative AV block that is not expected to
resolve after cardiac surgery
Third-degree and advanced second-degree AV block at any anatomic level associated with neuromuscular diseases with AV block,
such as myotonic muscular dystrophy, KearnsSayre syndrome, Erb dystrophy (limb-girdle muscular dystrophy), and peroneal
muscular atrophy, with or without symptoms
Second-degree AV block with associated symptomatic bradycardia regardless of type or site of block
Asymptomatic persistent third-degree AV block at any anatomic site with average awake ventricular rates of 40 bpm or faster if
cardiomegaly or LV dysfunction is present or if the site of block is below the AV node
Second- or third-degree AV block during exercise in the absence of myocardial ischemia
Recommendations for permanent pacing in chronic bifascicular block
Advanced second-degree AV block or intermittent third-degree AV block
Type II second-degree AV block
Alternating bundle-branch block
Recommendations for permanent pacing after the acute phase of myocardial infarction
Persistent second-degree AV block in the HisPurkinje system with alternating bundle-branch block or third-degree AV block within
or below the HisPurkinje system after ST-segment elevation MI
Transient advanced second- or third-degree infranodal AV block and associated bundle-branch block. If the site of block is
uncertain, an electrophysiological study may be necessary
Persistent and symptomatic second- or third-degree AV block
Recommendations for permanent pacing in hypersensitive carotid sinus syndrome and neurocardiogenic syncope
Recurrent syncope caused by spontaneously occurring carotid sinus stimulation and carotid sinus pressure that induces ventricular
asystole of more than 3 sec
Recommendations for permanent pacing after cardiac transplantation
Persistent inappropriate or symptomatic bradycardia not expected to resolve and for other Class I indications for permanent pacing
Recommendations for permanent pacemakers that automatically detect and pace to terminate tachycardias
Reasonable for symptomatic recurrent SVT that is reproducibly terminated by pacing when catheter ablation and/or drugs fail to
control the arrhythmia or produce intolerable side effects
Recommendations for permanent pacing to prevent tachycardia
Sustained pause-dependent VT, with or without QT prolongation

SND, sinus node dysfunction; AV, atrioventricular; SVT, supraventricular tachycardia; VT, ventricular tachycardia; MI, myocardial infarction.
Adapted from the 2008 ACC/AHA/HRS guidelines for device-based therapy of cardiac rhythm abnormalities. Circulation 117:28202840, 2008
(Permission needed).

rate, all of which can be manipulated in order to optimize cap- performed quickly in emergency situations. To synchronize
ture and patient comfort [39]. pacing, most systems also require the placement of one to three
Initiation of transcutaneous pacing begins with place- additional electrodes to sense native QRS discharge.
ment of electrode pads. Modern systems usually employ self- A square-wave impulse is delivered over 20 to 40 millisec-
adhesive large-area (>80 cm2 ) electrode pads which are im- onds by the generator and is seen as a spike on its display. The
pregnated with a conducting gel. Polymer-based electrode pads relatively long pulse width attempts to reduce skeletal muscle
of low impedance are generally now preferred. Although the and cutaneous nerve stimulation while still maximizing thresh-
anteroposterior position is sometimes employed in hospital set- old of cardiac myocyte capture. Capture is achieved when each
tings, most commercial machines suggest anterolateral posi- pacing discharge is immediately followed by a wide QRS com-
tioning of pads to improve speed of application (see Fig. 43.2) plex of uniform morphology. Although most impulse genera-
and allow for continuous cardiopulmonary resuscitation with tors can produce output of up to 200 mA, most healthy subjects
chest compressions if necessary. When possible, removal of will capture between 40 and 80 mA [41]. The patient threshold
chest hair with shaving reduces impedance [40]. Pulling away is defined as the lowest output that yields consistent electrical
of hair follicles with extra pads is also effective and can be ventricular capture. In hospital settings, higher thresholds (up
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Chapter 43: Bradyarrhythmias and Temporary Pacing 461

Widespread use over the past three decades has established


the overall efficacy of transcutaneous pacing in the treatment of
bradyarrhythmia. In the largest single retrospective review of
clinical trials in 1985, Zoll reported an overall success rate that
approached 80% [41]. The use of newer electrode pads with
improved capture yield a performance rate of nearly 100%
when used in the very early and prophylactic treatment of brad-
yarrhythmias [44]. Timing is, of course, critical, and transcuta-
neous pacing for out of hospital asystolic arrest has been shown
to be of no benefit [45].

Complications
The safety profile of transcutaneous devices has been well es-
tablished over the past five decades, and suggests that its use is
remarkably well tolerated. The primary limitation in its use is
patient discomfort, and skin injury at contact site is the most
commonly reported complication [41]. Prolonged animal pac-
ing models have variably shown very small areas of focal my-
ocardial injury, although no such injury has been shown in
humans postmortem [41,42]. In normal individuals, transcu-
taneous pacing produces no measurable release of myoglobin,
myocardial creatine kinase, or lactate dehydrogenase [42]. Also
importantly, transcutaneous pacing has never been shown to in-
duce arrhythmia, even in patients in whom MI or transvenous
pacing precipitated ventricular tachycardia or ventricular fib-
rillation previously [41]. Taken together, transcutaneous pac-
FIGURE 43.1. External pacemaker/defibrillator (pulse generator).
ing has supplanted transvenous pacing as the initial modality
(Courtesy of ZOLL Medical Corporation.) for bradyarrhythmic treatment in the emergency setting, par-
ticularly when pacing is only needed for short durations and
patient comfort is not a primary consideration.
to 140 mA output or more) are commonplace and may due to
multiple etiologies. Suboptimal lead positioningparticularly
over boneas in the scapula, sternum, or spine, is an avoidable
Transvenous Pacing
cause of increased pacing threshold. Other factors which may Furman and Robinson first described placement of an elec-
elevate thresholds that are beyond operator control include pa- trode catheter into the right ventricle for the management of
tient body habitus or obesity, transient myocardial ischemia, high-grade conduction block in 1958 [46]. Transvenous elec-
trapped pericardial fluid, mediastinal air, significant emphy- trodes circumvent patient discomfort and offer a reliable means
sema, use of positive pressure ventilation, or anoxia from pro- of temporary pacemaker support in acute settings. Commonly
longed resuscitation efforts [41,42]. used catheters are either bipolar electrodes, usually steel or
By default, pacing mode in most machines is set at ventric- platinum-tipped, embodied in plastic which may be flexible
ular sensing, pacing, and inhibition in response to native ven- and associated with an inflatable balloon, or semirigid catheters
tricular conduction. Asynchronous pacing is usually only used which are deployed alone or with stylets. Most catheters have
during brady asystolic arrest, when cardiopulmonary resusci- relied upon passive-fixation, although active-fixation, screw-
tation may cause artifact, particularly during chest compres- in catheters with externalized pacemakers have also been re-
sions. Pacing rates of up to 180 bpm can also be achieved by cently employed for more prolonged temporary pacing require-
most machines, allowing for overdrive pacing in the treatment ments [47,48]. Preformed J-shaped catheters are also used
of tachycardia or shortening of QT interval as needed. Hemo- for placement into the atrial appendage, but are not usually
dynamic response, as measured by cardiac output and blood used in temporary pacemaking applications (see Fig. 43.3).
pressure augmentation, is comparable with or better than right Leads are attached to temporary pacemaker generators, which
ventricular endocardial transvenous pacing [43]. are generally constant-current output devices (see Fig. 43.4),

A B C

FIGURE 43.2. A, B: Positioning of transcutaneous electrode pads anteroposterior. C: Anterolateral positioning.


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462 Section III: Cardiovascular Problems and Coronary Care

FIGURE 43.3. A: Cardiac pacing catheters. Top: Balloon tipped, flow-directed wire. Middle: Standard
5-Fr pacing wire. Bottom: Atrial J-shaped wire. B: Example of a balloon-tipped lumened pacing catheter
with distal and proximal electrodes. [Swan-Ganz bipolar pacing catheter, courtesy of Edwards Lifesciences
LLC.]

FIGURE 43.4. Temporary atrioventricular demand pulse generators, FIGURE 43.5. Pattern of recorded electrogram at various locations in
older (left) and recent (right) models. Adjustable parameters on the the venous circulation. [From Harthorne JW, Eisenhauer AC, Steinhaus
older model include pacing mode (synchronous or asynchronous), ven- DM: Cardiac pacing, in Eagle KA, Haber E, De Sanctis RW (eds): The
tricular rate, ventricular current output (in milliamperes), atrial output Practice of Cardiology: The Medical and Surgical Cardiac Units at the
(in milliamperes), and atrioventricular interval (in milliseconds). The Massachusetts General Hospital. Boston, Little, Brown and Company,
newer model also allows atrial sensing. 1989, p 313, with permission.]
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Chapter 43: Bradyarrhythmias and Temporary Pacing 463

from within the right ventricle. The catheter is then advanced to


the right ventricular apex. After contacting the myocardium, a
characteristic pseudo-injury current appearance is seen (see
Fig. 43.6), representing catheter pressure against the ventricu-
lar wall and not actual injury to muscle. Figure 43.7 shows
a sketch of a right anterior oblique fluoroscopic projection
of proper positioning of both ventricular and atrial catheters.
Table 43.4 provides a summary outline for bedside positioning
of an electrode catheter in the right ventricle.

Complications
Transvenous pacing offers a reliable and stable means of car-
diac pacing, which is generally easier for patients to tolerate,
but associated with a greater risk of complications because of
its invasive procedural placement. Multiple studies have re-
FIGURE 43.6. Injury current indicating positioning of electrode ported on complications associated with transvenous pacing,
against right ventricular wall. [Reproduced with permission of OHL although there has been marked variability in defining and mea-
Bing, MD.] suring what constitutes a complication [35,4954]. In a repre-
sentative group of three studies, the overall complication rate
ranged from 13% to 18% (see Table 43.5) [49,50,54]. Of these,
although externalized pacemakers have been used for longer induction of ventricular arrhythmia is the most immediately
periods of electrical support in the setting of systemic infection
[47,48]. Standard pulse generators deliver output ranging from
0 to 20 mA at a pulse width of 1 to 2 milliseconds. Optimal pac- TA B L E 4 3 . 4
ing thresholds are considered less than 1 mA, as thresholds usu-
ally escalate with patient movement or catheter dislodgement. BEDSIDE POSITIONING OF A TEMPORARY
In addition, thresholds may be affected by medications, elec- ELECTRODE CATHETER
trolyte disturbances and ischemia; therefore, devices are usually
set to discharge at an output of three to five times threshold. Setup
Multiple approaches for placement have been described, in- Sterile preparation (gowns, gloves, masks, drape, hat)
cluding internal jugular, subclavian, femoral, and antecubital Equipment (pacing electrode catheter, pulse generator,
fossa vein routes [35,4954]. Of these, the right internal jugu- surface electrodes, sheath)
lar vein is preferred for ease as well as the lowest rate of com- Connections
plication [55]. A stereotypic transition of ECG recordings has V1 surface electrode connects to distal electrode
been observed when advancing the catheter from the internal Proximal electrode catheter connects to positive pole of pulse
jugular or subclavian vein to the superior vena cava (see Fig. generator
43.5) [56]. Atrial- (or P wave) dominated ECG recordings are
seen in the high and low right atrium. The QRS is readily seen Testing components
Inflate balloon to test integrity
Document V1 recordings when inserting electrode catheter
into the sheath
Procedure
Carefully advance electrode catheter 15 cm and inflate
balloon
Observe V1 transition with advancement of catheter
(see Fig. 43.5)
Atrial (P wave) dominant
Ventricular (QRS) dominant
Injury current
Stop advancing once injury current is detected
Pacing preparation
Confirm proximal electrode is connected to positive pole of
pulse generator
Disconnect distal electrode from V1 surface lead and connect
to the negative pole of the pulse generator
Pacing
Attempt pacing at 10 mA with the highest sensitivity
Observe capture
Determine thresholds and set output two to three times
threshold (generally 5 mA)
Postprocedure
FIGURE 43.7. Sketch of fluoroscopic projection of catheter posi- Document distance electrode is within the sheath
tion. Ao, aorta; RV, right ventricle; SVC, superior vena cava [From Confirm position with a chest radiograph
Harthorne JW, Eisenhauer AC, Steinhaus DM: Cardiac pacing, in
Eagle KA, Haber E, De Sanctis RW (eds): The Practice of Cardiology: Routine care of pacemaker and site, including:
The Medical and Surgical Cardiac Units at the Massachusetts Gen- Pacing parameters (threshold, rate, sensitivity, output)
eral Hospital. Boston, Little, Brown and Company, 1989, p 315, with Skin site (observing for infection)
permission.]
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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464 Section III: Cardiovascular Problems and Coronary Care

TA B L E 4 3 . 5 TA B L E 4 3 . 6
COMPLICATIONS OF TEMPORARY TRANSVENOUS MOST COMMON COMPLICATIONS OF TEMPORARY
PACINGa PACING WIRE INSERTION ACROSS 15 STUDIES AND
3,747 PATIENTS [55]
Donovan Lumia Austin
Complication [50] [49] [54] Complication Average rate (%) Range (%)

Ventricular tachycardia/ 4.8 8.5 6.0 Failure of access 15 640


fibrillation Failure to place lead 10 525
Other arrhythmias NR 2.8 NR Sepsis 9 218
Phlebitis NR 4.2 5.0 Arterial puncture 4 06
Pulmonary embolism NR 1.4 3.0 Lung/myocardium puncture 2 04
Hematoma/bleeding or 4.8 1.4 4.0 Arrhythmias 1 02
arterial puncture
Perforation 1.9 2.1 4.0 Adapted from: McCann P: A review of temporary cardiac pacing
Abscess at site NR 0.7 3.0 wires. Indian Pacing Electrophysiol J 7:4049, 2006.
Pneumothorax 1.0 NR NR
Pacing failure with 1.0 NR NR
ventricular asystole potential complications and meticulous technique can lower
Diaphragm pacing 2.9 NR NR risks for what may be a lifesaving procedure.

a
All numbers are percentages.
NR, not reported. SUMMARY
Cardiac bradyarrhythmias represent a heterogeneous group
life threatening, with myocardial puncture, pneumothorax, ar- of rhythm disturbances of impulse generation or conduction.
terial bleeding and induction of infection leading to sepsis also These may include potentially reversible etiologies such medi-
being potentially deadly. Lead dislodgment can occur in a sub- cation overdose and electrolyte disturbance, to progressive con-
stantial number of patients within the first 48 hours of use, duction system defect and irreversible ischemia. Appropriate
requiring replacement or re-positioning of the temporary pace- treatment hinges upon the identification of the etiology of brad-
maker wire. yarrhythmia in order to identify and eliminate precipitants if
In a recent exhaustive narrative review, average rates of possible while initiating appropriate medical therapy. In situ-
complications were compiled for 3,747 patients across 15 stud- ations of hemodynamic embarrassment, a concurrent assess-
ies of cardiac pacing (see Table 43.6) [55]. Rates of infection ment is made of whether temporary cardiac pacing may be
were complications in as high as half of all procedures reported required to bridge patients through acute instability and re-
in some studies. In addition, older patients were at higher risk covery or to permanent pacemaker placement. In the intensive
for suffering a complication, but that risks were lower when care unit, commonly used modalities include transcutaneous
temporary pacemaker placement was performed by a specialist pacing and transvenous pacing, which should be selected based
rather than a general practitioner. Given these findings, fluoro- on balance of patient comfort, potential for complication, and
scopic placement of transvenous catheters by experienced per- duration of use.
sonnel is preferred. In addition, prophylactic antibiotics should
be considered for all temporary cardiac pacemakers, as these
measures have already been shown to reduce the risk of infec- ACKNOWLEDGMENTS
tions after permanent pacemaker insertion [57].
With these concerns in mind, temporary transvenous pacing The authors acknowledge the contributions of Drs. Glenn
may still be required to definitively treat bradyarrhythmia and Meininger and Hugh Calkins to the version of this chapter
support patients through hemodynamic collapse. Attention to as published in the previous edition.

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34. Roden DM: A practical approach to torsade de pointes. Clin Cardiol 20:285 56. Bing OH, McDowell JW, Hantman J, et al: Pacemaker placement by electro-
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P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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466 Section III: Cardiovascular Problems and Coronary Care

CHAPTER 44 HOW TO MANAGE CARDIAC


PACEMAKERS AND IMPLANTABLE
DEFIBRILLATORS IN THE INTENSIVE
CARE UNIT
MELANIE MAYTIN AND USHA B. TEDROW

electrical stimulus delivered near the lead tip. Electrical stimuli


INTRODUCTION can be delivered in many ways depending on how the device
is programmed. Pacing nomenclature is standardized to easily
Cardiac device technology has made great advancements since communicate information regarding the device and the pac-
the introduction of the first implantable pacemaker in 1958. ing mode (Table 44.2). Pacing algorithms are best understood
Since then, the number of cardiac device implants continues to as a function of timing cycles. A pacemaker operates like a
increase annually as a result of the aging of the general popu- timer with programmable intervals to coordinate all sensed and
lation, expanding indications for device therapy, and ongoing paced events. Nontracking modes of pacing (AAI, VVI, DDI)
innovation in the technology of cardiac pacing and defibrilla- deliver electrical impulses at set intervals (lower rate limit) un-
tion. As a result, many patients presenting to the intensive care less a sensed electrophysiologic cardiac event occurs in the ap-
unit (ICU) with noncardiac illness may have implanted cardiac propriate chamber before the end of the programmed interval
devices. This chapter aims to briefly review basic cardiac device (in which case the timer resets, Fig. 44.3). Dual-chamber de-
function and programming with emphasis on device malfunc- vices programmed to a tracking mode can provide pacing at
tion and troubleshooting. A discussion of the indications for the programmed lower rate or track-sensed intrinsic conduc-
permanent pacing, defibrillator or resynchronization therapy tion up to a programmed upper rate limit. There is no sensing
is outside the scope of this text; for additional information re- in asynchronous pacing modes (AOO, VOO, DOO) and elec-
garding these topics, the reader is referred to the American Col- trical stimuli are produced at programmed intervals unaffected
lege of Cardiology/American Heart Association/Heart Rhythm by intrinsic conduction.
Society 2008 Guidelines for Device-Based Therapy of Cardiac
Rhythm Abnormalities [1].
Magnets
The placement of a magnet over a device affects pacemakers
and defibrillators differently. Application of a magnet to a pace-
GENERAL DEVICE MANAGEMENT maker will cause the reed switch to close and result in asyn-
chronous pacing. The pacing rate is company-specific with a
Normal Device Function and Special different rate once battery depletion has occurred. Thus, place-
ment of a magnet over the device can assist with the determina-
Considerations tion of battery status and device identification. If exposure to
electromagnetic interference (EMI) is anticipated, positioning a
Identification of the type of device is critical in interpretation magnet over the device can prevent inappropriate pacing inhi-
of its function. Although the patients would ideally be able to bition. On removal of the magnet, the pacing mode will revert
provide information regarding the type of device that has been to the originally programmed settings, and, in general, formal
implanted (pacemaker, implantable cardioverter defibrillator device interrogation is not required. In contrast, application of
(ICD), cardiac resynchronization device, etc.) or carry a de- a magnet to a defibrillator will disable all antitachycardia ther-
vice identification card with them at all times, this is frequently apies but will not affect the pacing mode. Therefore, magnets
not the case in hospitalized patients. Substantial device infor- can be used to prevent inappropriate therapies due to supraven-
mation can be gleaned from a chest radiograph, including the tricular tachycardia (SVT), lead fracture, or EMI. On removal
lead configuration, the type of device, abnormalities in lead of the magnet, defibrillator therapies will be restored, and, in
position or integrity, and even the device manufacturer (Fig. general, formal device interrogation is not required.
44.1AC). Identification of the device manufacturer is essential
if formal device interrogation or reprogramming is planned as
each device company uses different software and programmers
Electromagnetic Interference
to communicate with their respective devices (Fig. 44.2). The In hospitals, many potential sources of EMI exist. Sources
overwhelming majority of devices implanted are manufactured of electromagnetic energy that could possibly interfere with
by one of three companies, and patient device information and device function include magnetic resonance imaging (MRI),
technical support are available 24 hours a day (Table 44.1). electrocautery, defibrillation, radiation therapy, neurostimu-
The device system consists of a pulse generator or bat- lators, TENS units, radiofrequency ablation, electroconvul-
tery, logic circuits, and pacing or defibrillator lead(s). All sive therapy, video capsule endoscopy, extracorporeal shock
implantable cardiac devices have programmable pacemaker wave lithotripsy and therapeutic diathermy [2,3]. EMI expo-
functions. These devices can both sense intrinsic electrical de- sure most commonly results in inappropriate inhibition or trig-
polarization and excite myocardial tissue through an artificial gering of pacing stimuli, inappropriate ICD tachyarrhythmia
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 44: How to Manage Pacemakers and Defibrillators in the ICU 467

FIGURE 44.1. Information regarding implantable cardiac de-


vices can be gained from chest radiograph. A: Dual-chamber
pacemaker with leads in the RA and RV. B: Single-chamber,
dual-coil defibrillator with high-voltage conductors in the RV
and SVCRA junction. C: Cardiac resynchronization device
with leads in the RA, RV, and CS. These devices may or may not
C have defibrillator function. RA, right atrium; RV, right ventricle;
SVC, superior vena cava; CS, coronary sinus.

FIGURE 44.2. Many cardiac devices


are marked with a radiopaque code
that specifically identifies the man-
ufacturer and model of the device.
A: Medtronic ICD with magnified
view of radiopaque code (inset). The
manufacturer is identified by the
Medtronic logo at the extreme left of
the code and the model by the three
letter code that represents the engi-
neering series number. B: Boston Sci-
entific ICD with magnified view of
radiopaque code (inset). The manu-
facturer and model are identified by
A B the radiopaque codes GDT and
104, respectively.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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468 Section III: Cardiovascular Problems and Coronary Care

TA B L E 4 4 . 1 tracking at the upper rate limit in response to a rapid atrial


tachyarrhythmia. Once the device has mode switched, it will
DEVICE MANUFACTURERS CONTACT remain in a nontracking mode until the atrial rate has fallen
INFORMATION below the mode switch threshold for a specific number of inter-
vals. This algorithm is very useful for patients with paroxysmal
Medtronic 1.800.MEDTRONIC atrial arrhythmias (e.g. SVT, atrial fibrillation or atrial flutter).
Boston Scientific 1.800.CARDIAC The atrial rate at which mode switch occurs is programmable
St. Jude Medical 1.800.PACEICD in most devices and the feature can even be programmed
Biotronik 1.800.547.0394 off.
Sorin Group 1.800.352.6466
Line Management
The placement of central venous catheters in cardiac device
detection and therapy and reversion to an asynchronous pacing patients warrants special consideration. Depending on the lo-
mode (noise-reversion mode). cation and age of the device and the planned location of
Inappropriate inhibition of ventricular pacing can be catas- central venous access, a number of potential complications
trophic in the pacemaker-dependent patient; similarly atrial can occur. Reported complications associated with central
oversensing with inappropriate ventricular tracking could re- venous catheters in cardiac device patients include lead dam-
sult in a myriad of symptoms including heart failure exacerba- age from needle puncture [4], lead dislodgement, and in-
tion, hypotension, or angina. Improper ICD tachyarrhythmia appropriate ICD therapies [5]. In addition, central venous
detection due to EMI could potentially be arrhythmia-inducing stenosis as a consequence of prior cardiac device implanta-
as a result of unsynchronized inappropriate shock delivery dur- tion may present a challenge to central venous catheter place-
ing the vulnerable period of repolarization. Noise-reversion ment ipsilateral to the device [6]. Cardiac device infections
mode is an algorithm that reverts transiently to asynchronous and device-related endocarditis represent a particularly seri-
pacing in response to rapid frequency signals. The algorithm is ous hazard of indwelling central venous catheters necessitating
designed to protect against inappropriate inhibition of pacing removal of the entire device system [7]. Central venous ac-
when high-frequency signals are sensed. Although this algo- cess should be performed contralateral to the device whenever
rithm is present in all pacemakers regardless of manufacturer, possible.
this is not the case for ICDs. Less frequently, EMI can result
in reprogramming of the device parameters or permanent cir- Magnetic Resonance Imaging
cuitry or lead damage. When EMI exposure is unavoidable, cer-
tain measures can be taken to minimize the potential risk. For The likelihood that patients with cardiac devices will require an
example, pacemaker or defibrillator patients requiring surgery MRI is high [8] but this imaging modality is not without risks
with electrocautery should have a magnet placed over the de- in these patients. The potential hazards of magnetic resonance
vice during the operation. Other forms of EMI (e.g. MRI, ra- imaging in cardiac device patients include movement of the
diation therapy) carry substantial risk and may prompt the device, programming changes, asynchronous pacing, activa-
revision or removal of the entire cardiac device system prior tion of tachyarrhythmia therapies, inhibition of pacing output,
to planned exposure. Care should be taken to avoid sources and induced lead currents that could lead to heating and car-
of EMI in device patients or, if exposure to EMI cannot be diac stimulation [9], resulting in altered pacing and defibrilla-
avoided, at a minimum, measures should be taken to minimize tion thresholds, device damage, asystole, arrhythmias, or even
potential harm with consideration of device interrogation fol- death [10]. Although an implantable cardiac device remains a
lowing exposure. strong relative contraindication to MRI, certain centers have
developed protocols for performing MRIs in cardiac device
Mode Switch patients [11] and MRI-safe pacemakers are being developed.
If an MRI is the only diagnostic imaging option in a cardiac
Mode switch is a programmable pacing algorithm that auto- device patient, imaging at 1.5 Tesla with appropriate program-
matically changes the pacing mode to a nontracking mode ming and monitoring can likely be undertaken safely with care-
in response to a sensed atrial arrhythmia. The purpose of ful assessment of the riskbenefit ratio on a case-by-case basis
this algorithm is to prevent inappropriately fast ventricular [1114].

TA B L E 4 4 . 2
PACING DESIGNATION

NASPE/BPEG Generic (NBG) Code

Position I II III IV V

Category Chamber(s) pace Chamber(s) sensed Response to Programmability, rate Antitachy-arrhythmia


sensing modulation function(s)
Letters used O-None O-None O-None O-None O-None
A-Atrium A-Atrium T-Triggered P-Simple Programmable P-Pacing (antitachy-
V-Ventricle V-Ventricle I-Inhibited M-Multiprogrammable arrhythmia)
D-Dual (A + V) D-Dual (A + V) D-Dual (T + I) C-Communicating S-Shock
R-Rate modulation D-Dual (P + S)
Manufacturers S-Single S-Single
designation only (A or V) (A or V)
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 44: How to Manage Pacemakers and Defibrillators in the ICU 469

FIGURE 44.3. Timing of events in various pacing modes. AAI is an atrial nontracking mode of pacing
that provides backup atrial pacing at the programmed lower rate limit. Similarly, VVI is a ventricular
nontracking mode of pacing that provides backup ventricular pacing at the programmed lower rate limit.
DDD is a dual-chamber mode of pacing that can both inhibit and trigger events in both the atrium and
the ventricle. AS, atrial-sensed event; AP, atrial-paced event; VS, ventricular-sensed event; VP, ventricular-
paced event; LR, lower rate limit.

External Defibrillation tion. Cardiac device-related infection requires prompt removal


of the entire device system for complete treatment unless sig-
In the event of a cardiac arrest or hemodynamically unstable
nificant comorbidities preclude extraction [7,18]. Although no
arrhythmia in a patient with an implantable cardiac device,
specific vegetation size has been established as a contraindica-
resuscitative efforts should proceed as per guidelines without
tion to transvenous extraction, most experts agree that vegeta-
deviation. Defibrillation or cardioversion can result in perma-
tions greater than 3 cm in size are better treated surgically [7].
nent damage to the cardiac device; to minimize these risks,
Patients with device-related endocarditis require a minimum
the defibrillation pads should be placed at least 10 cm from
of six weeks of intravenous antibiotics and pose a particular
the pulse generator [15]. Other potential risks of external de-
problem with respect to the timing of re-implant in pacemaker-
fibrillation include device reprogramming [16] and myocardial
dependent patients.
damage at the interface with the lead resulting in an acute rise in
threshold [17]. Following defibrillation or cardioversion, car-
diac devices should be interrogated formally to insure proper
function and programming. Again, the low potential risk of Pacemaker Malfunction
damage to the device should not impede usual and necessary
resuscitative efforts for the patient. Oversensing
Sensing problems are one of the most common causes of pace-
maker malfunction (Table 44.3). Oversensing is defined as the
Infection sensing of physiologic or nonphysiologic events that should not
Cardiac device-related infection encompasses a disease spec- be sensed. Consequently, oversensing can lead to inappropriate
trum from pocket infection to device-related endocarditis. The inhibition of pacemaker output (Fig. 44.5). Physiologic events
clinical manifestations of cardiac device-related infection are that can be the cause of oversensing include far-field P waves,
protean and can range from pain at the implant site without wide QRS complexes, T waves, and myopotentials, either pec-
cutaneous manifestations to minor erythema or swelling of the toral or diaphragmatic. Typically, oversensing due to physio-
device pocket (Fig. 44.4A) to overt erosion of the system (Fig. logic events can be overcome by decreasing the programmed
44.4B) to device-related endocarditis (Fig. 44.4C) [18,19]. In sensitivity. Nonphysiologic oversensing may be the result of
the absence of bacteremia, systemic manifestations and leuko- EMI or hardware problems such as loose setscrew or lead dis-
cytosis are rare. Cultures of the device leads yield the highest lodgement or fracture and will likely require device revision
results and, Staphylococci are the primary pathogen identified to correct. Oversensing and failure to pace in a pacemaker-
[20]. A high index of suspicion is warranted in a patient with dependent patient can be catastrophic. Application of a mag-
implanted pacemaker or ICD and signs and symptoms of infec- net over the device will change the device to an asynchronous
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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470 Section III: Cardiovascular Problems and Coronary Care

FIGURE 44.4. Different manifestations of device-related infections.


A: Swelling and erythema suggest pocket infection although local signs
of inflammation may be absent. B: Erosion of either the lead(s) or
the device by definition is a manifestation of infection. In this example,
the pocket appears swollen with areas of erythema and a pacing elec-
trode (arrow) is seen eroding through the skin at the inferior margin
of the pocket. C: Device-related infection could result in bacteria, veg-
etations and sepsis. Here, transesophageal echocardiography demon-
C strated a large vegetation (arrow) adherent to the atrial pacing lead
and seen to prolapse across the tricuspid valve.

pacing mode and insure more reliable delivery of pacing until changes at the lead-myocardial border although this has be-
a formal evaluation can be performed. come less relevant clinically with the advent and widespread
use of steroid-eluting leads. A rise in capture threshold can be
Undersensing overcome by increasing the pacemaker output. Other causes
of elevated capture thresholds include myocardial fibrosis or
In contrast, undersensing occurs when the device fails to sense infarction near the exit of the pacing stimulus, metabolic
intrinsic events. This results in the generation of unnecessary derangements (specifically, hyperkalemia, acidemia and hyper-
pacemaker impulses and overpacing. Undersensing may be glycemia), and certain medications. Class Ia, Ic, and III antiar-
a result of alterations in electrogram amplitude of physiologic rhythmic drugs [2127] can increase capture thresholds as can
events or may represent hardware failure. Antiarrhythmic drug mineralocorticoids and hypertonic saline [28]. If the capture
therapy, myocardial infarction, and metabolic derangements threshold exceeds the maximal programmable output, this is
can alter electrogram amplitude transiently or permanently. termed exit block. Primary hardware problems such as lead dis-
Undersensing may be potentially corrected by changing the lodgement, perforation or fracture, and battery depletion can
programmed sensitivity. Other etiologies of undersensing are all result in noncapture. A chest radiograph can help diagnose
similar to those of noncapture (lead dislodgement, perfora- specific lead issues (Fig. 44.7AC). Formal pacemaker interro-
tion, or fracture). Asynchronous pacing modes, due to EMI gation or magnet application can identify battery depletion.
or battery depletion, can mimic undersensing on surface elec-
trocardiogram.
No Output
Noncapture The complete absence of pacemaker stimuli despite magnet
application suggests complete battery depletion or generator
Noncapture occurs when electrical impulses emitted from the damage. Damage to the generator can occur rarely as a result
device fail to capture myocardium. The surface electrocar- of direct trauma [29] or external defibrillation [15].
diogram will demonstrate pacing stimuli without evidence of
capture (Fig. 44.6). Loss of capture can be intermittent or per-
manent, but often necessitates device revision. Causes of non-
Pacemaker-Mediated Tachycardia
capture can be divided into changes in capture threshold and Pacemaker-mediated tachycardia (PMT) refers to any sustained
hardware malfunction. The capture threshold can rise in the tachyarrhythmia that is dependent on continued pacemaker
first 4 to 6 weeks following lead implant due to inflammatory participation in the circuit. Classically, the term PMT is used to
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 44: How to Manage Pacemakers and Defibrillators in the ICU 471

TA B L E 4 4 . 3
TROUBLESHOOTING PACEMAKER MALFUNCTION

Problem Etiology Causes Management

Failure to pace, no Oversensing Physiologic events Reprogram.


PPM stimuli P, R, or T waves Avoid EMI sources.
Myopotentials Device revision.
Nonphysiologic events
EMI
Lead fracture
Loose setscrew
Failure to pace with Noncapture Elevated threshold Reprogram, if
PPM stimuli Exit block possible. Correct
MI, fibrosis reversible causes.
Medications May require device
Electrolytes revision.
Hardware failure Device revision.
Lead dislodgement
Lead fracture
Lead perforation
Battery depletion
Inappropriate Undersensing Low EGM amplitude Reprogram, if
pacing Low at implant possible. Correct
MI, fibrosis reversible causes.
Medications May require device
Electrolytes revision.
Lead dislodgement Lead revision
Lead fracture Lead revision
ERI Replace PPM
Noise reversion Reprogram

EMI, electromagnetic interference; EGM, electrogram; ERI, elective replacement interval; PPM, pacemaker.

describe an endless loop tachycardia in dual-chamber devices [36]. Catheter ablation is effective in the treatment of electri-
consisting of ventricular pacing, retrograde atrial activation, cal storm and can be considered for electrical storm despite
appropriate sensing and triggered ventricular pacing perpet- chronic antiarrhythmic therapy and for refractory cases [37].
uating the tachycardia (Fig. 44.8). PMT should be suspected
when ventricular pacing occurs at the programmed maximum
tracking rate of the device. The PMT circuit can be interrupted Ineffective Defibrillation
with magnet application and the arrhythmia terminated. Successful defibrillation occurs when a critical mass of my-
ocardium is successfully depolarized and depends on shock
vector, lead position, and the electrical milieu. The optimal
three-dimensional orientation of the ICD shock vector should
DEVICE-SPECIFIC deliver energy uniformly throughout the left ventricle. The vec-
CONSIDERATIONS tor is dependent on the position of the high-voltage coils in the
right ventricle (RV) and superior vena cava (SVC)-right atrial
(RA) junction and the active can in relation to the left ventricle.
Implantable Cardioverter Defibrillator Typically, the RV coil is the cathode and the SVCRA coil and
ICD can form the anode with current traveling from cathode
Electrical Storm to anode.
Electrical or ventricular tachycardia (VT) storm is defined as Implantable defibrillators can fail to deliver effective defib-
three or more episodes of VT or ventricular fibrillation within a rillation therapy in certain situations. Elevated defibrillation
24-hour period. When a patient presents with electrical storm, thresholds (DFT) can occur as a result of metabolic derange-
suppression of the arrhythmias are of paramount importance. ments, myocardial ischemia, pneumothorax, hypoxia, multiple
Identifying the trigger can be difficult [30] but attempts should defibrillations, drug therapy, delays in arrhythmia detection,
be made to identify and correct potentially treatable causes and device hardware malfunction (Table 44.5). Immediate
(Table 44.4). Repeated defibrillator therapy is painful and management should consist of external defibrillation and treat-
highly stressful, can cause heightened sympathetic tone and re- ment of potential reversible causes. Long-term management
sult in early battery depletion, myocardial ischemia/stunning, may require device revision or cessation/addition of specific
and recurrent ventricular arrhythmias [31,32]. Thus, initial antiarrhythmic medications.
treatment should consist primarily of sympathetic blockade
with beta-blockers and anxiolysis with benzodiazepines. Amio-
darone is often the antiarrhythmic agent of choice [33,34]. Re-
Inappropriate Therapies
fractory cases may require intubation and deep anesthesia [35]; Inappropriate therapies are common in patients with im-
stellate ganglion blockade can be considered in extreme cases plantable defibrillators regardless of indication [38] and are
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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472 Section III: Cardiovascular Problems and Coronary Care

FIGURE 44.5. Dual-chamber defibrillator with evidence of ventricular oversensing. The top panel demon-
strates atrial (AP) and ventricular (VP) sequential pacing with the intermittent absence of ventricular pacing
stimuli (asterisks) following atrial paced events. The bottom panel represents the intracardiac electrograms
from the same device with ventricular oversensing of atrial events (arrows). When intrinsic ventricular
conduction does occur (arrowheads), the device incorrectly labels the event as VF (arrowheads) or a
ventricular event that because of timing falls into the programmed ventricular fibrillation detection zone.

FIGURE 44.6. Surface electrocardiogram with intermittent loss of ventricular capture. There is appropri-
ate atrial sensing (AS) and tracking as evidence by pacing stimuli at a fixed interval following the P wave
but intermittent failure of ventricular output to capture the myocardium (asterisks). Evidence of varying
degrees of fusion between intrinsic conduction and ventricular pacing is also observed (arrows).
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 44: How to Manage Pacemakers and Defibrillators in the ICU 473

A B

FIGURE 44.7. Chest radiography can identify device hardware


problems. A: Lead fractures (arrow) can sometimes been seen on
x-ray and detailed attention should be paid to the leads along their
entire length when a hardware problem is suspected. B: Overt
lead perforation can be diagnosed by x-ray. In this example, the
entire distal electrode of the defibrillator lead extends beyond
the cardiac silhouette (arrow). C: Chest radiography can also
confirm lead dislodgement. PA and lateral films of a dual-chamber
pacing system with the ventricular lead in the right ventricular
outflow tract demonstrate dislodgement of the atrial lead. There
is evidence of atrial lead dislodgement in the PA view with the
distal electrode pointing inferiorly and no visible slack on the lead
with absence of the typical J-shaped appearance. Atrial lead
dislodgement is confirmed by the lateral view that demonstrates
C the distal electrode of the lead residing below the tricuspid valve
annulus.

associated with significant morbidity and mortality [39,40].


Common causes of inappropriate therapies include SVT, ven-
tricular sensing problems, lead failure, and EMI. The detection
algorithms of ICDs are based primarily on heart rate, and any
ventricular-sensed event that exceeds the programmed detec-
tion rate will trigger ICD therapy. Supraventricular discrimi-
nators related to arrhythmia onset, cycle length stability and
electrogram morphology are also programmable but reduce
inappropriate therapies only slightly [41,42]. Repeated inap-
propriate ICD therapies in hemodynamically stable patients
should prompt magnet application or device deactivation with
back-up external defibrillation available and definitive treat-
ment directed at the underlying rhythm or problem.
The most common cause of inappropriate defibrillator ther- FIGURE 44.8. Pacemaker-mediated tachycardia (PMT). A premature
apy is atrial fibrillation although sinus tachycardia and other ventricular complex (PVC) occurs in a patient with a dual-chamber
pacemaker. The PVC results in retrograde conduction back to the
SVTs can result in inappropriate therapies. Surface electro- atrium that is subsequently tracked by the ventricular lead and in-
cardiogram and clinical status may aid with the diagnosis cessant tachycardia ensues. Retrograde atrial activation is sensed by
if formal interrogation is not immediately available. The de- the pacemaker because it falls outside the postventricular atrial refrac-
vice should be inactivated and treatment directed at the un- tory period (PVARP). One means of eliminating PMT is to extend the
derlying atrial arrhythmia. Ventricular sensing problems also PVARP.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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474 Section III: Cardiovascular Problems and Coronary Care

TA B L E 4 4 . 4 or tachycardia at the time of defibrillation. Device hardware


problems cannot be overcome with reprogramming. The ICD
CAUSES OF ELECTRICAL STORM should be deactivated until the system can be revised. Similarly,
EMI can produce noise and result in inappropriate therapies.
Acquired long QT
Decompensated heart failure
Electrolyte disturbances Withdrawal of Care
Fever/sepsis
Hyperthyroidism Patients with ICDs and end-stage heart failure or other fatal
Lead dislodgement/position illness warrant special consideration. Successful defibrillation
Medication noncompliance may prolong life but it cannot prevent death. In addition, re-
Myocardial ischemia peated ICD shocks in a patient with end-stage disease may
Myocarditis cause unnecessary pain and anxiety. Defibrillation can be de-
Psychologic stressors activated in ICDs without deactivating pacemaking functions.
Substance abuse Discussions regarding ICD deactivation occur rarely even in pa-
Sympathomimetics tients with do-not-resuscitate orders [43]. It is important that
patients and their families understand that deactivation of de-
fibrillator therapies is always an option [44].

result in inappropriate therapies when other electrical events


(P waves, T waves, wide QRS) are misinterpreted as a ven-
Cardiac Resynchronization Therapy
tricular event. This double counting is erroneously inter- (Biventricular Pacing)
preted as a tachyarrhythmia and prompts inappropriate ICD
therapy. Ventricular oversensing may be transient as a result Cardiac resynchronization therapy (CRT) improves symptoms,
of metabolic derangements (e.g., peaked T waves with hyper- decreases hospitalizations, assists with reverse remodeling of
kalemia) or may sometimes be successfully eradicated with the left ventricle, and reduces mortality in patients with symp-
reprogramming of the device although some sensing prob- tomatic heart failure, severe left ventricular dysfunction, and
lems may require device revision. Hardware problems such as mechanical dyssynchrony (QRS >120 ms) [4548]. Ventricu-
lead fracture, insulation break, lead dislodgement, or a loose lar resynchronization aims to achieve myocardial coordination
setscrew may result in noise and short ventricular cycle lengths through left ventricular preexcitation ideally at the site of lat-
that can be mistakenly detected as VT. The surface electrocar- est activation. This can be achieved through an endovascular
diogram is extremely useful and will demonstrate sinus rhythm approach with left ventricular lead placement via coronary si-
nus cannulation or epicardially with a direct surgical approach
(typically via left lateral thoracotomy). Approximately 70% of
CRT patients demonstrate clinical improvement with reduc-
tion in symptoms [49,50] and even fewer show improvement
TA B L E 4 4 . 5 in left ventricular function [51].
EFFECT OF COMMON DRUGS ON DEFIBRILLATION
THRESHOLDS Loss of Resynchronization
Drug Effect on DFT Achieving resynchronization appears dependent not only on
stimulating the ventricle at the site of latest activation but also
Antiarrhythmics providing reliable biventricular pacing. There appears to be
Amiodarone a threshold effect of CRT related to frequency of biventric-
Disopyramide ular pacing. A recent retrospective analysis demonstrated a
Dofetilide significant decrease in hospitalizations and mortality at biven-
Ibutilide tricular pacing above 92% [52]. Among CRT responders,
Flecainide loss of resynchronization can result in recurrent symptoms,
Lidocaine diminished functional capacity, repeat hospitalization, and
Mexilitine significant hemodynamic alterations. Although formal device
Quinidine interrogation is necessary to assess the degree of biventricular
Procainamide pacing over the long-term, careful observation of the teleme-
Propafenone try monitor often can provide significant insight. Similarly, the
Sotalol 12-lead electrocardiogram can identify the site of ventricular
Beta-blockers stimulation and can be used to detect loss of biventricular pac-
Atenolol ing (Fig. 44.9A, B). Atrial arrhythmias with intact ventricular
Carvedilol conduction exceeding the programmed lower rate of the CRT
Propranolol device are the most common reason for failure to achieve suf-
ficient resynchronization. Other potential reasons for subop-
Calcium channel blockers timal biventricular pacing include elevated pacing threshold,
Diltiazem lead fracture, or lead migration to an unfavorable location.
Verapamil Common reasons for a lack of response to CRT are lead lo-
Others cation, suboptimal programming and underlying narrow QRS
Digoxin [53]. If the left ventricular pacing lead is not stimulating a late
Fentanyl activation site in the basal posterolateral left ventricle, the de-
Ranolazine gree of biventricular pacing is irrelevant. The electrocardio-
Sildenafil gram and chest radiograph are useful in identifying issues with
left ventricular lead placement.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 44: How to Manage Pacemakers and Defibrillators in the ICU 475

FIGURE 44.9. A, B: Electrocardiographic assessment of pacing site. A: Right ventricular apical pacing
with left bundle branch morphology and superior frontal plane axis. B: In contrast, biventricular stimu-
lation with right bundle morphology in V1 and QS waves in leads I and avL.

Summary Attention to and understanding of the implanted device as a


critical portion of the patients acute care is warranted. Early
In the modern era, patients with implantable pacemakers, involvement of electrophysiologist colleagues in the care of crit-
defibrillators and cardiac resynchronization devices are in- ically ill patients especially with device malfunction or infection
creasingly commonly admitted to the care of an intensivist. is prudent.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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476 Section III: Cardiovascular Problems and Coronary Care

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P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 45: Mechanical Support for Heart Failure 477

CHAPTER 45 MECHANICAL SUPPORT FOR


HEART FAILURE
JEFFREY J. TEUTEBERG AND FIRAS E. ZAHR

During the past two decades the incidence of cardiogenic shock sion [6]. Mechanical unloading of the left ventricle leads to a
has not significantly declined despite important progress in the decrease in the severity of mitral regurgitation, less pulmonary
management of patients with acute myocardial infarction and congestion, and a reduction in pulmonary arterial hyperten-
advanced heart failure [1,2]. Cardiogenic shock is character- sion, all of which, in turn, can result in improved right ven-
ized by persistent hypotension with systolic arterial pressures tricular (RV) function. Partial support pumps provide several
typically less than 80 mm Hg and marked reduction of cardiac liters of flow to augment the reduced native ventricular contri-
index (<2 L per minute per m2 ) in conjunction with elevated bution to the total output, whereas full support pumps provide
left ventricular (LV) filling pressures and evidence of end-organ upwards of 6 to 7 L of flow with the native heart contributing
hypoperfusion. Patients may present in shock as a complica- little to the total output. Restoration of forward flow and the
tion of acute myocardial infarction, cardiac surgery, acute my- normalization of filling pressures also reduces neurohormonal
ocarditis, or an acute decompensation of chronic heart failure. activation, with attendant benefits on cardiorenal function; as
Although the mortality of patients presenting with acute my- a result, temporary VAD support may allow reverse ventricu-
ocardial infarction and cardiogenic shock declined during the lar remodeling and sufficient recovery of ventricular function
1990s, the 1-month mortality remains nearly 50% despite ag- to permit explantation in selected patients [7].
gressive efforts at reperfusion therapy [25]. In many cases of
cardiogenic shock, medical therapy alone may be inadequate,
and the patient may require temporary or even permanent me- Biologic
chanical support. The proper application of mechanical cir-
culatory support (MCS) requires knowledge of the underly- The hemodynamic benefits of mechanical circulatory support
ing mechanism of heart failure, understanding of the potential with a LV assist device (LVAD) are also associated with fa-
benefits and limitations of both medical and device therapy, vorable structural changes within the cardiac myocytes and
familiarity with the full range of devices available for support, extracellular matrix. In studies of isolated human cardiac my-
and perhaps most critically, careful selection of the appropriate ocytes, LVAD support increased the magnitude of contraction,
timing for intervention. shortened the time of peak contraction, and reduced the time
to 50% relaxation. In addition, responses to beta-adrenergic
stimulation were greater in isolated myocytes after LVAD sup-
MECHANICAL CIRCULATORY port. This suggests that mechanical unloading might reverse the
downregulation of beta-adrenergic receptors and improve car-
SUPPORT diac responsiveness to inotropic stimulation [815]. In vivo,
Over the past five decades, mechanical circulatory support mechanical unloading with an LVAD is known to be associ-
technology has evolved substantially from partial temporary ated with alteration of gene and protein expression within the
support with intra-aortic balloon counterpulsation to a broad cardiac myocyte [16,17], a reduction in nuclear size and DNA
array of ventricular assist devices (VADs) capable of provid- content, and a reduction in fibrosis and collagen content within
ing long-term complete support for one or both ventricles. In the cardiac extracellular matrix [10,11].
the 1990s, extensive experience with bridging patients to trans-
plantation spurred the evolution from bulky extracorporeal de-
vices to smaller, implantable designs, which allowed patients to SELECTION OF APPROPRIATE
be discharged from the hospital and have substantial improve-
ments in functional status and quality of life. More recently, the
MECHANICAL SUPPORT
prior generations of larger pulsatile pumps have been super- The clinical application of MCS grew from early experience
seded by the introduction of smaller, more durable continuous with its application as temporary support in the operating room
flow devices with superior survival and fewer adverse events. to supporting patients for months until transplant. A broad ar-
ray of different ventricular support devices is now available
(Table 45.1). Broadly speaking, the devices may be configured
BENEFITS OF MECHANICAL for isolated right ventricular (RVAD), left ventricular (LVAD),
or biventricular (BiVAD) support and for short-term (bridge
CIRCULATORY SUPPORT to recovery or bridge to decision), short-term (bridge to trans-
plant), or long-term (destination therapy) support [18]. Some
Hemodynamic devices are extracorporeal or paracorporeal in location, with
cannulae traversing the skin allowing for inflow and outflow of
As the left ventricle begins to fail, cardiac output falls and in- blood, whereas others are totally implantable with the pump
tracardiac filling pressures rise. The main goals of MCS are to and the cannulae housed in the thoracic and/or abdominal cav-
decompress the failing ventricle and augment systemic perfu- ity with only a single percutaneous line supplying the power
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478 Section III: Cardiovascular Problems and Coronary Care

TA B L E 4 5 . 1
APPROVED MECHANICAL CIRCULATORY SUPPORT DEVICES

TemporaryLV support

Description Approved devices Advantages Disadvantages

Extracorporeal Cannulated from LV apex Abiomed BVS 5000 Relatively easy to implant Unable to ambulate
pulsatile to ascending aorta
Continuous Catheter-based axial flow Impella 2.5 Percutaneous placement in Partial support device
flow Centrifugal TandemHeart cath lab Current indication for
Often used emergently System Rapid placement high-risk PCI
with resuscitation Centrimag Place in catheterization lab Unable to ambulate
ECMO without Leg ischemia from large
Rapid surgical placement bore cannula
Used with oxygenator Requires familiarity with
when pulmonary transseptal cannula
concomitant pulmonary placement
support required Unable to ambulate
Usually surgically placed
PermanentLV support
Description Approved devices Advantages Disadvantages

Extracorporeal Inflow cannula from LV Thoratec PVAD Ease of implantation Total of two large cannula
pulsatile and outflow cannula to Abiomed AB5000 traversing skin
ascending aorta External pumps
Implantable Pump implanted in the HeartMate XVE Requires only an aspirin, Less durable if duration of
pulsatile abdomen or Thoratec IVAD no Coumadin support >912 months
preperitoneally, Approved as DT BSA 1.5 m2
allowing increased Durable INR 2.53.5
mobility and ability to Less portable peripherals
discharge
Continuous Pump implanted in the HeartMate II and Reduced size and noise Difficult to assess BP and
flow thoracic cavity with MicroMed DeBakey Much greater durability pulse due to lack of
only one moving part. than pulsatile devices pulsatility
Better adverse event profile Suck-down caused by
than pulsatile pumps over unloading ventricle
Permanentbiventricular support/TAH
Extracorporeal Two pumpsone Thoratec PVAD Easy to insert for unstable Two pumps with a total of
supporting the RV and patients four cannula transversing
one supporting the LV, the skin
but native heart External pumps
remains in place
Intracorporeal Native heart removed AbioCor and Removes cardiac tissues Available only in select
completely SynCardia which may contribute to centers
CardioWest inflammation and be Not applicable to most
susceptible to clots, patients
arrhythmias or
interference with pump

LV, left ventricle; PCI, percutaneous coronary intervention; ECMO, extracorporeal membrane oxygenation; TAH, total artificial heart; BSA, body
surface area; BP, blood pressure; RV, right ventricle.

and providing the connections to the external control systems. allows for substantially smaller pump profiles and longer pump
Early generation devices were volume displacement pumps, life.
which had a volume chamber sequentially filled and emptied of
blood, mimicking the native heart and providing pulsatile flow.
However, the need for a volume displacement chamber resulted Cannulation
in a larger pump size and also required more moving parts re-
sulting in mechanical wear and shorter pump life. The current VADs are typically implanted in parallel with the native right-
generation of devices no longer has a displacement chamber, or left-sided circulation. For long-term LVADs, the pump in-
but rather has a continuously rotating impeller. This results flow is from a cannula placed directly into the LV apex and
in a continuous flow of blood and thus limited pulsatility, but the pump outflow is a cannula that is anastomosed to the
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Chapter 45: Mechanical Support for Heart Failure 479

FIGURE 45.1. Representative left ventricular assist devices. (Right) Continuous flow LVAD (HeartMate
II). Cardiac output is maintained by the continuous rotation of an impeller. (Left) Pulsatile flow LVAD
(HeartMate XVE). Cardiac output is maintained by the sequential filling and emptying of a volume
displacement chamber and unidirectional blood flow is provided with the use of valves before and after
the displacement chamber. [From Wilson SR, Givertz MM, Stewart GC, et al: J Am Coll Cardiol 54:1647
1659, 2009, with permission.]

ascending aorta just distal to the aortic valve. Pulsatile sys-


tems typically have valves in the inflow and outflow cannulae, Continuous Flow
whereas continuous flow devices do not. For percutaneous sys-
tems, the pumps may be placed across the aortic valve and into In contrast to pulsatile flow pumps, continuous flow pumps
the left ventricle or into the left atrium via transcatheter punc- have a continuously rotating impeller which produces forward
ture of the interatrial septum. RVADs typically have inflow flow. The left ventricle is continuously and actively unloaded
from the right atrium rather than the RV apex as RV apical and therefore the left ventricle rarely can fill to the point where
cannulation typically provides less reliable flow. The venous it can eject blood during systole. Thus, the patient has little pul-
blood may also be accessed from the cavae or femoral veins. satile contribution from their native ventricles and hence has
Outflow is directed to the main pulmonary artery just distal to little to no pulse pressure, but rather have a mean blood pres-
the pulmonic valve through either direct or transvenous can- sure. Patients supported with continuous flow LVADs therefore
nulation. require Doppler ultrasound to assess their blood pressure. Con-
tinuous flow pumps are generally one of two major types: axial
or centrifugal flow. Axial flow pumps have the impeller rotat-
ing in the same plane as the blood flow, whereas centrifugal
pumps accelerate the blood perpendicularly to the axis of in-
Pulsatile Flow flow. They typically have only one moving part (the impeller)
which is magnetically or hydrodynamically suspended result-
Early-generation VADs are volume displacement pumps which ing in little wear over time. Given the size and wear consid-
fill and empty asynchronously with the cardiac cycle creating erations, among others, continuous flow pumps are now the
pulsatile arterial flow. The pulsatile pumps mostly fill pas- pump of choice for long-term support. The internal and ex-
sively or have limited ability to augment their filling; thus, ternal components of representative pulsatile and continuous
the beat-to-beat filling of the pump depends partially on the flow pumps are as seen in Figure 45.1.
cardiac cycle. Although most of the blood volume entering Most recent data suggests that implantation of a
the left ventricle is diverted into the pump, the left ventricle continuous-flow LVAD, as compared with a pulsatile-flow de-
does occasionally fill enough to eject and contribute to the vice, significantly improved the probability of survival free of
total cardiac output. In settings of hypovolemia, the pump stroke and reoperation for device repair or replacement at
will fill less quickly and thus the pump rate will slow down, 2 years in patients with advanced heart failure in whom medical
the converse is true in the setting of hypervolemia, thus main- therapy had failed and who were ineligible for transplantation.
taining a relatively constant state of decompression of the left In addition, the 2 year actuarial survival with an LVAD was
ventricle. significantly better with a continuous-flow device than with a
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480 Section III: Cardiovascular Problems and Coronary Care

pulsatile-flow device. The continuous-flow LVAD was also as- of vWF multimers results in bleeding from pre-existing AVMs
sociated with significant reductions in the frequency of adverse or the lack of pulsatile flow predisposes to the development
events and the rate of repeat hospitalization, as well as with an of AVMs [2729]. Although most patients have a demonstra-
improved quality of life and functional capacity [1922]. ble loss of vWF multimers, only a minority of patients develop
bleeding. For those who are awaiting transplant, bleeding re-
quiring transfusion carries the additional risk of sensitization
Extracorporeal Membrane Oxygenation to human leukocyte anitgen (HLA) antigens that may limit the
pool of suitable donor organs [30].
Extracorporeal membrane oxygenation (ECMO) can provide
pulmonary or cardiopulmonary support for up to a week or
more. Blood is withdrawn from the circulation via an inflow Infection
cannula to an extracorporeal continuous flow pump, an oxy-
genator, and then back to the patient through an outflow can- Aside from the infection risks associated with surgery and in-
nula. There are two basic types of ECMO: venovenous (VV) dwelling lines postoperatively, there is the additional chronic
and venoarterial (VA). In VV ECMO, the blood is withdrawn risk associated with the presence of the VAD itself and the asso-
from a large central or peripheral vein (jugular or femoral) and ciated driveline or cannulae. However, sepsis from any source
oxygenated blood is returned via another large vein. Thus, VV can result in seeding of interior of the VAD or its components,
ECMO does not provide hemodynamic support, but rather pul- which may necessitate more urgent and higher risk transplant
monary support. For VA ECMO the inflow is typically via the or even device replacement [31]. Vegetations on LVAD pros-
femoral vein and the outflow is typically through the femoral thetic valves may also be a source of thromboembolism [32].
artery and thus provides both oxygenation and mechanical cir-
culatory support. VA ECMO is most commonly used in the set-
ting of severe shock in the setting of acute infarction, fulminant Thromboembolism and Stroke
myocarditis or cardiac arrest or after a failure to wean from car-
diopulmonary bypass. In the setting of a failure to wean from Embolism may result from the pump due to inadequate anti-
bypass, the intraoperative cannulation that was used for car- coagulation, the cardiac chambers due to arrhythmias such as
diopulmonary bypass can be attached to the ECMO circuit, atrial fibrillation, or may arise from the native vasculature as a
rather than having new cannula placed peripherally. Outside result of the patients preexisting vascular atherosclerosis. The
the setting of the operating room, both VV and VA EMCO can overall incidence of ischemic stroke varies greatly with type of
be rapidly instituted even at the bedside, as either configuration device, however with the current generation devices the rate is
can be achieved through peripheral access, but should only be 0.09 per patient-year overall and 0.05 per patient-year after 30
performed by experienced personnel. days [33]. Maintenance of goal INR is critical to minimize the
risk of thromboembolism.

COMPLICATIONS
Although the focus of this chapter is the preoperative assess-
INDICATIONS
ment and management of patients being considered for MCS, MCS may be appropriate for either short-term (<1 week) or
knowledge of some of the common postoperative complica- long-term support of patients with heart failure and shock. In
tions of MCS are necessary to understand the implications of the majority of cases, long-term MCS is intended as a hemo-
some of these preoperative considerations. The three most com- dynamic bridge to subsequent cardiac transplantation (BTT)
mon are bleeding, infection, and thromboembolism. [34]. For patients who are not candidates for transplant, an
LVAD may be used for long-term support (destination therapy,
DT) [19]. The only two devices that have been approved for DT
Bleeding in the United States are the HeartMate XVE, and more recently
Thoratecs HeartMate II LVAD [19,22]. Occasionally, patients
Placement of an intracorporeal pump requires a sternotomy are placed on MCS in anticipation of ventricular recovery and
and cardiopulmonary bypass. The degree of perioperative device explantation (bridge-to-recovery), as in selected patients
bleeding can be affected by preexisting coagulopathy, liver con- with postcardiotomy shock or acute heart failure due to poten-
gestion, and prior sternotomies or other concomitant correc- tially reversible causes (e.g., fulminant myocarditis) [34].
tive surgeries at the time of MCS. Most current-generation de-
vices, whether temporary or permanent, require anticoagula-
tion with heparin after post-operative bleeding subsides and
then chronically with warfarin and, depending on the center, UNIVENTRICULAR VERSUS
an antiplatelet agent(s). Most pulsatile devices have mechani- BIVENTRICULAR SUPPORT
cal prosthetic valves requiring an INR of 2.5 to 3.5, whereas
some of the current generation continuous flow devices may Selection of the appropriate device for MCS depends initially
only require an INR of 1.5 to 2 [23]. Thus, there is a risk of on the type of support that is required. Most patients present-
continued or new onset bleeding throughout the duration of ing with acute heart failure or shock predominantly have LV
support, but current devices have a risk of bleeding requiring failure and may be candidates for isolated LV support with an
transfusion of about 0.85 per patient year beyond 30 days, LVAD. Successful LVAD implantation, however, relies heavily
which is a substantial improvement in comparison to previous on confirmation of adequate native RV function, since RV func-
generation pulsatile devices [24,25]. However, the continuous tion is required for LVAD filling [35]. For patients with con-
flow pumps present a unique risk for gastrointestinal bleeding. comitant, severe RV dysfunction, biventricular support may
The high shear stress on the blood from the impeller can cause be necessary. Although recent experience suggests that selected
destruction of large multimers of von Willebrand factor (vWF), BiVAD patients can be successfully discharged to home, out-
which results in a picture of acquired von Willebrands disease comes are generally poorer than with LVAD alone, perhaps in
[26,27]. Bleeding risk is mostly manifest from gastrointestinal part due to greater severity of illness and end-organ dysfunc-
arteriovenous malformation (AVMs), it is unknown if the loss tion amongst patients presenting initially with biventricular
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Chapter 45: Mechanical Support for Heart Failure 481

failure [36]. Since BiVAD treatment is currently available function, early referral and implantation of patients with ac-
only for patients who are candidates for eventual cardiac celerating heart failure symptoms despite medical therapy for
transplantation, up-front BiVAD support should only be con- evaluation is especially important.
sidered in transplant-eligible patients with prolonged shock,
giant cell-myocarditis, refractory ventricular tachyarrhyth-
mias, or a high likelihood of postoperative RV failure. Even
with the current generation of continuous flow LVADs, there SELECTION OF CHRONIC HEART
is an approximately 7% incidence of RV failure requiring an
RVAD postoperatively, highlighting the need for careful assess-
FAILURE PATIENTS FOR
ment of RV function prior to VAD implantation [3742]. In LONG-TERM MCS
select centers, explant of the native heart and implantation of
a total artificial heart (TAH) may provide an alternative to the Cardiac
use of BiVADs [43].
RV Function
URGENT VERSUS ELECTIVE Assessment of RV function is critical when considering MCS
particularly in those who are being implanted with the intent
SUPPORT of long-term support. An LVAD alone is preferred for long-
term support and only LVADs are approved for DT, but it is
Urgent MCS not a viable strategy if the RV cannot adequately fill the LVAD
[36]. RV function can be acutely affected by the primary eti-
Urgent mechanical support may be necessary in a subgroup ology of the myopathy such as with ischemia in the presence
of patients presenting with acute, medically refractory car- of acute infarction, inflammation in the setting of myocardi-
diogenic shock (e.g., acute myocardial infarction, fulminant tis, or persistent ventricular arrhythmias. The RV can also be-
myocarditis, acute valvular incompetence). In these subjects, come dysfunctional as a result of chronic elevations of LV filling
time for comprehensive medical and surgical evaluation is lim- pressures and/or mitral valve pathology, which results in pul-
ited, and the focus is on rapid hemodynamic stabilization and monary hypertension and thus increased RV afterload. Lastly,
restoration of end-organ perfusion. Historically, because of other processes that may exacerbate pulmonary hypertension,
widespread availability and ease of implantation, the IABP has such as hypoxic lung disease, sleep apnea, chronic thromboem-
been a cornerstone of therapy; however, for many patients an bolic disease, or pulmonary vasculopathy, can also contribute
IABP may be inappropriate (e.g., those with severe peripheral to RV dysfunction. Chronic severe RV dysfunction with con-
arterial disease or aortic insufficiency (AI)) or inadequate in the comitant increases in right atrial pressures and tricuspid regur-
setting of profound cardiac dysfunction. Increasingly, stabiliza- gitation further exacerbates liver and renal dysfunction, leads
tion for such patients may be accomplished with temporary or to gut edema with poor absorption of medications and nutri-
percutaneous VADs (e.g., TandemHeart, Impella, CentriMag) ents, and results in hypotension and an inability to tolerate
or with urgent institution of extracorporeal membrane oxy- diuresis, beta-blockade, and ACE inhibition [49].
genation (ECMO) [44]. Particularly for those patients with LV mechanical support is generally beneficial to RV func-
cardiogenic shock complicated by progressive hypoxemia de- tion, with chronic unloading of the left ventricle resulting in
spite adequate ventilation, ECMO, if instituted early, can be a a reduction in pulmonary pressures and thus, RV afterload.
lifesaving measure [45,46]. As such, transfer to a specialized However there may be deleterious effects of an LVAD on RV
medical center with experience in cardiac transplantation or function, particularly when RV function is marginal. Profound
MCS should be considered as soon as medically feasible. Once unloading of the LV, particularly with continuous flow devices,
stabilized with MCS, patients can be either weaned gradually can result in shift of the septum away from the RV and thus
over time or, as appropriate, be transitioned to more permanent decrease the septal contribution to RV output. The RV may
devices for long-term support (if irreversible end-organ damage also struggle to accommodate the increased venous return as a
has not already occurred). In general, critically ill patients have result of the improved cardiac output from the LVAD [50,51].
better outcomes if they are stabilized and undergo implanta- Echocardiography provides valuable information about
tion of long-term MCS on an urgent rather than emergent basis, overall RV size and function, the degree of tricuspid regur-
largely due to the extremely high rate of perioperative compli- gitation and can give estimates of pulmonary arterial systolic
cations amongst patients presenting multisystem organ failure pressures. However, functional assessments of RVEF are quite
[24]. subjective and even a fairly normal appearing RV on echocar-
diography may have little functional reserve [52]. Invasive
hemodynamic assessment with a pulmonary arterial catheter is
Elective MCS therefore essential to decision making regarding the adequacy
of RV function. The degree of elevation in the right atrial pres-
For patients with advanced heart failure, MCS on a more elec- sure (RA), especially in relation to the wedge (W) pressure can
tive basis is becoming the preferred strategy for optimizing out- be quite revealing. One would expect high RA and W pressures
comes for patients whether they are BTT or DT. End-stage in the setting of heart failure, but with a normally functioning
heart failure is characterized by progressive functional decline RV, the RA pressures are relatively lower than the W and thus
and repeated heart failure hospitalizations which significantly the RA/W ratio typically remains less than 0.5. With the onset
impacts both resource utilization and quality of life [47,48]. Al- of RV dysfunction, the RA pressures increase out of propor-
though support with intravenous inotropic agents (in hospital tion to the left-sided pressures and the RA/W ratio increases.
or at home) may provide temporary relief, these agents are as- A high right atrial pressure in the setting of low pulmonary
sociated with an increased risk of adverse outcomes including arterial pressures and low RV stroke work index are also con-
arrhythmia and sudden death [20]. Furthermore, patients may cerning for the presence of severe RV failure [53].
still experience progressive functional decline and end-organ Given the morbidity associated with RV failure post-LVAD,
dysfunction during long-term inotropic support. Since elective a number of investigators have sought risk factors for postim-
VAD implantation is most successful when instituted prior to plantation RV dysfunction. Univariate predictors for RV fail-
the onset of irreversible end-organ (e.g., liver or kidney) dys- ure include RV stroke work index, small BSA, and mechanical
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482 Section III: Cardiovascular Problems and Coronary Care

ventilation [40,41]. Multivariate predictors include the need ure state resolves. However, patients with persistent ventricular
for preoperative circulatory support, female gender, and a non- dysrhythmias despite reasonable filling pressures are at poten-
ischemic etiology of heart failure [40]. Researchers at the Uni- tially higher risk of recurrence or persistence of these arrhyth-
versity of Michigan developed a risk score for RV failure based mias post-MCS and thus are more likely to need biventricular
on vasopressor requirement, an AST 80 IU, total bilirubin support.
2 mg per dL, creatinine 2.3 mg per dL that is predictive
of RV failure as well as overall survival [54]. However, there Aortic Valve
are many limitations to these studies including being based on
The cardiac assessment of patients being considered for MCS
single-center studies, small sample sizes, and are mostly based
should focus on other morphologic features of the heart other
on prior generation pulsatile devices.
than the LV and RV function. The presence and quantification
A recent study of 484 patients examined the predictors of
of AI is particularly important. Blood from the left ventricle
RV dysfunction in patients receiving a current generation con-
empties into the device and is then pumped into the ascending
tinuous flow device (HeartMate II) across multiple centers as
aorta just distal to the aortic valve. The presence of significant
a bridge to transplantation. Multivariate predictors of RV fail-
AI will result in ineffectual forward flow as the blood that was
ure were preoperative ventilator support (OR 5.5), CVP/W >
pumped into the aorta is regurgitated back into the ventricle
0.63 (OR 2.3), and BUN > 39 (OR 2.1). Patients without RV
only to reenter the device, be pumped into the aorta, and regur-
failure also had significantly better survival at 6 months (89%
gitate into the ventricle once again in a blind loop. Moderate or
vs. 67%, p < 0.001) and shorter lengths of stay (22 vs. 32
worse AI should prompt aortic valve repair, replacement with
days, p < 0.001). This study, unlike other prior studies, also
a tissue valve, or oversewing of the aortic valve. With adequate
investigated the effects of intraoperative factors which might
decompression by the LVAD, the left ventricle generates very
impact RV function. Those who required an RVAD required
little effective forward flow and hence rarely opens the aortic
more units of packed red blood cells (14.3 vs. 5.6, p < 0.03)
valve. In patients with mechanical aortic prostheses, this lack of
and had twice the incidence of reoperation for bleeding (40%
flow across the valve may result in the formation of thrombosis
vs. 19%, p < 0.04) [55].
and subsequent embolism [59]. Thus, mechanical aortic valves
Management of RV failure is similar to that of LV failure,
are either replaced with tissue valves at the time of surgery or
decreasing excess preload, inotropy, and reducing afterload.
are oversewn.
RV preload should be reduced with aggressive diuresis and, if
needed, mechanical volume removal if there is a renal limita-
tion to diuresis. The dysfunctional RV may need slightly more
Other Cardiac Abnormalities
preload to maintain output, but a goal should be to reduce The presence of large atrial or ventricular septal defects should
the RA pressure to less than 13 mm Hg. Inotropy is often be ruled out as these will need to be addressed during the time
needed for LV support as well, but is often equally important of implantation. Mitral regurgitation essentially resolves post-
to maintaining RV output [50]. Milrinone is typically the in- MCS with adequate LV decompression, but significant mitral
otrope of choice for RV support in the setting of concomitant stenosis can impede LVAD filling and should be addressed at
pulmonary hypertension due to its vasodilatory properties. Af- the time of implantation [60]. The degree of tricuspid regur-
terload is addressed through strategies to reduce elevated pul- gitation should be quantified as severe tricuspid regurgitation
monary pressures. Reducing the left sided filling pressures is is a predictor of poor outcomes with LVAD alone [61]. LV
the first and most important therapeutic targets and can be ac- thrombus can form in the setting of acute ischemia or with
complished through a combination of diuresis, inotropy, IABP, chronic LV dysfunction. Such thrombi are usually located in
and even a temporary LVAD. Patients must have adequate oxy- the LV apex, which is the site of cannulation for the LVAD.
genation to avoid hypoxic pulmonary vasoconstriction and if Although the ventricle is routinely inspected before insertion
intubated positive end expiratory pressure should be minimized of the cannula, knowledge of the presence of thrombus preop-
[56]. Nitric oxide may be considered in the intubated patient, eratively is nevertheless important as retained thrombus may
but such patients may be too ill to consider LV support alone. systemically embolize or, more ominously, be sucked into the
There is little evidence for the use of other vasodilators such impeller of a continuous flow pump resulting pump dysfunc-
as prostaglandins and some evidence that such therapies may tion or failure. For patients with congenital heart disease it is
be deleterious in the setting of LV failure [57]. A summary of important to establish the anatomical position of the systemic
the management of RV function and the various organ systems ventricle and aorta as well as the type and location of any previ-
discussed below is as seen in Table 45.2. ous corrective surgeries. Complex congenital heart disease may
necessitate placement of the pump or inflow/outflow cannulae
in atypical positions.
Arrhythmias
Ventricular tachyarrhythmias are reasonably common in the
setting of acutely decompensated heart failure. Many patients Noncardiac
with chronic heart failure will have a history of ventricular
tachycardia or have an implantable cardioverter defibrillator Other chronic medical conditions, many of which are exacer-
(ICD) with or without resynchronization therapy [58]. Aside bated by acute heart failure, should be optimized if possible
from their impact on the patients stability in the acute phase of prior to implantation of long-term MCS. Patients must be as-
their presentation, the persistence of ventricular tachyarrhyth- sessed for signs of infection and if found treated aggressively
mias has implications for outcomes on mechanical support. prior to implant. Active infection at the time of implantation
The presence of sustained ventricular tachycardia or ventric- can be catastrophic as septicemia can result in device infec-
ular fibrillation during LVAD support can substantially affect tion which may be chronically suppressed but rarely cured
RV function, particularly in the setting of borderline RV func- with antibiotic therapy. If the pump or the pocket in which
tion. Although ventricular tachyarrhythmias are not typically it sits becomes infected, the only recourse is urgent transplant,
lethal in the setting of LVAD support alone, they will fairly rou- if indicated, as device exchanges in these situations often re-
tinely result in lower pump output, hypotension, and recurrent sult in recurrent infection [62]. Renal dysfunction at the time
symptoms. For patients with an ICD they may also result in fre- of presentation is common from a variety of causes: poor re-
quent ICD discharges. Preoperative ventricular tachyarrhyth- nal perfusion, high right atrial pressures, preexisting renal dys-
mias in the setting of substantially elevated filling pressures function, high doses of diuretics, and the adverse neurohor-
or acute ischemia often resolve after MCS as the heart fail- monal milieu of heart failure. It is certainly advantageous if the
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Chapter 45: Mechanical Support for Heart Failure 483

TA B L E 4 5 . 2
ORGAN SYSTEM REVIEW OF CANDIDATES FOR MECHANICAL CIRCULATORY SUPPORT

Organ system Review Organ system Review

LV dysfunction
Preload Diuresis Pulmonary disease Avoid hypoxia
Mechanical volume removal Attempt to quantify extent/
Cardiac output Support with inotropy severity of lung disease
IABP or temporary support as Liver disease Occult liver disease in the
needed presence of persistently high
After load Treat hypertension, if present right atrial pressures
IABP Ultrasound/CT scan to assess
RV dysfunction Assess with invasive for cirrhosis
hemodynamics Coagulation Stop any unneeded
Preload Diuresis anticoagulants/antiplatelets
Mechanical volume removal Review for history of
Inotropy Milrinone if concomitant hypercoagulable state
pulmonary hypertension Vascular disease Review history
Afterload Decreasing left-sided filling Confirmatory ultrasound/CT
pressures scanning
Milrinone Nutrition Screen with prealbumin
Avoiding hypoxia Nutritional support

Arrhythmias Rate control Surgical


Antiarrhythmics Identify ASD/VSD
Cardioversion if hemodynami- Number of prior sternotomies
cally tenuous. Location and number of prior
Persistent ventricular bypass grafts
tachyarrhythmia despite Congenital abnormalities
adequate treatment of left Prior cardiac surgeries
heart failure may need Intracardiac thrombus
consideration for BiVADs Mitral stenosis

Aortic valve Assess for AI Other limitations


Presence of mechanical valve? Emotional Careful assessment and
support
Noncardiac Physical Ability to care for and utilize
Infection Aggressive assessment and device
treatment Cognitive Understanding device
Renal dysfunction Decrease high right atrial Social Support system available
pressures Financial Adequate resources as both
Inotropy or IABP inpatient and outpatient
Avoid nephrotoxic agents,
contrast

patient can be stabilized with inotropy, IABP, or even tempo- uncommon with chronic heart failure, especially in the setting
rary mechanical support to allow for renal recovery. Improve- of poor RV function with persistently high right atrial pressures
ment of renal function is often seen with restoration of cardiac or those with Fontan circulation [60]. These patients may have
output and resolution of the heart failure state after MCS, but is significant hepatic dysfunction without substantial baseline ab-
not the rule, especially when the patients are implanted in the normalities of AST, ALT, or total bilirubin. There should be a
setting of significant renal dysfunction [63,64]. Renal failure low threshold to screen such patients with ultrasonography or
requiring dialysis after MCS remains a highly morbid event, CT or even liver biopsy to assess hepatic architecture for signs
likely reflecting the level of illness entering the surgery as well of cirrhosis. If there is evidence of cirrhosis then early involve-
as an additional, persistent nidus of infection due to the need ment of hepatologists is essential. Patients with marginal hep-
for vascular access [65]. atic function frequently have massive transfusion requirements
Intrinsic pulmonary disease also has a number of implica- during implantation and not infrequently have acute hepatic
tions for long-term MCS. Advanced lung disease impacts mor- failure postoperatively. Careful management of antiplatelet and
tality and morbidity from the implantation surgery itself as well anticoagulant therapy around the time of VAD implant may be
as the ability to rehabilitate and post-operative functional sta- critical to minimizing the risk of perioperative bleeding. Exten-
tus. Hypoxic pulmonary vasoconstriction from intrinsic lung sive carotid or peripheral vascular disease may increase the risk
disease may also exacerbate preexisting pulmonary hyperten- of extracardiac vascular events following MCS, and must be
sion. Severe chronic pulmonary disease with an FEV1 of less evaluated appropriately with preoperative noninvasive testing
than 1 L is should raise concerns about a patients suitability [60]. In patients who present acutely, nutrition is not often
for MCS [60]. Intubation and mechanical ventilation prior to a pressing issue, but nutritional impairment in patients with
implantation is also a strong predictor of poor outcomes [38]. chronic heart failure can be quite profound and low BMI is a
Hepatic dysfunction is occasionally a result of shock from acute risk factor for poor outcomes [66]. Poor nutrition impacts T-
decompensation, but chronic occult hepatic dysfunction is not cell function and is another risk factor for infection and poor
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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484 Section III: Cardiovascular Problems and Coronary Care

wound healing postoperatively. For patients at nutritional risk


supplemental feeding may be of some use, but should not delay
implantation when MCS is indicated.

SURGICAL
Whenever patients are being considered for MCS the surgi-
cal team should be involved, not only to help assess a pa-
tients suitability for support, but also allow them time to
properly survey the patient for additional factors which may
impact outcomes. The number of prior sternotomies will im-
pact the ease of surgical approach, the operative time, the risk
of postoperative bleeding, and perhaps even the overall can-
didacy for MCS. The presence and degree of AI, the pres-
ence of mechanical valves, the number and location of prior
bypass grafts, the presence of intraventricular thrombus, and
the details of congenital abnormalities and subsequent surgi-
cal corrections should be determined and communicated to the FIGURE 45.2. Competing outcomes analysis of patients with a con-
surgical team as previously noted. The details of past surgi- tinuous flow left ventricular assist device as a bridge to transplant.
cal ventricular reconstruction should be sought, as these surg- [From Pagani FD, Miller LW, Russell SD, et al: Extended mechanical
eries usually involve the LV apex, the site of inflow cannulation circulatory support with a continuous-flow rotary left ventricular assist
for all long-term LVADs, and may present significant technical device. J Am Coll Cardiol 54:312321, 2009, with permission.]
challenges.

to transplant that may require a higher risk, emergent LVAD


OTHER CONSIDERATIONS or biventricular support, becoming too ill for either transplant
or mechanical support, or death. Proceeding with MCS early
Aside from the many and varied medical and surgical consider- allows for surgery to be performed when the patient is less
ations are emotional, physical, and social considerations. The ill followed by a lower risk transplant once the patient is re-
acute nature of many patients illness often precludes a detailed habilitated. Certain patients may be expected to have a short
assessment of such issues, but for nonemergent situations ad- wait for transplantation based on their size, blood type, and
dressing these issues prior to implantation is ideal. Physical level of sensitization and therefore the disadvantages of wait-
limitations that may impact the patients ability to care for the ing for transplant may be minimized. Others may have clear
device such as the manual dexterity to change batteries or hear indications for early MCS such as persistent pulmonary hyper-
alarms are a critical part of such a review. Adequate cognitive tension not responsive to medical therapy [68]. Unfortunately
ability is needed to understand the importance of the device most patients do not have such a clear delineation of risk and
and its components, the ability to troubleshoot problems, and determining the optimal timing of MCS can be quite difficult.
recognize when to ask for assistance. The emotional where- However, there is an emerging evidence base that supports the
withal to adapt to the device, its implications, potential lim- earlier institution of MCS.
itations, and adverse events is also important to maximizing Prior reticence to institute MCS was based upon results us-
long-term outcomes and quality of life. Lastly, patients must ing the prior generation of pulsatile LVADs with 6- and 12-
have an adequate social support network; although having an month survival of approximately 75% and 60%, respectively.
implanted VAD does not typically involve around the clock In contrast, the newer generation nonpulsatile pumps have
supervision, there must be a background of reliable support 6- and 12-month survival of 82% and 73%, respectively [33]
for assistance in an emergency and for long-term emotional (Fig. 45.2). Furthermore, these devices are also associated with
support. a much more favorable adverse event profiles and given their
smaller size are applicable to almost the entire cohort of trans-
plant eligible patients. When examining the survival of pa-
TIMING tients supported with MCS much of the mortality is early
and attributable to patient selection, with the sickest patients
When patients present to the intensive care unit with shock preimplantation having the worst outcomes [36]. This has lead
and are subsequently stabilized with aggressive medical ther- researchers to attempt to quantify this operative risk to improve
apy the decision to transition to MCS rests on the expectation patient selection.
of improvement in the patients condition. For those who re- Several risk prediction models are available for patients with
ceived an intervention, such as revascularization, waiting to see chronic systolic heart failure. The Heart Failure Survival Score
the impact of this intervention on the patients clinical status is comprised of clinical, laboratory data, and exercise data [69].
is reasonable in the absence of further clinical deterioration. The Seattle Heart Failure Model incorporates a much wider
Many patients, however, will not have a readily identifiable or array of clinical and laboratory variables and does not require
treatable proximate cause of their deterioration. For those who an exercise test. However, these models were derived from a
are eligible or are already listed for transplantation, the risk of much less critically ill population and have not been validated
continued medical therapy awaiting transplantation must be in patients who are being considered for mechanical circula-
weighed against the risk of proceeding with MCS [67]. The tory support [70]. Risk prediction models for patients under-
advantages of waiting for transplantation in the setting of sta- going LVAD exist, but are limited in that they describe risk
ble, yet critical illness are an increased likelihood of receiving attributable to device that is no longer used [71], are from a
an organ due to a higher status, avoiding a second surgery, previous era of MCS support [72], or only examined patients
and the potential morbidity and mortality of MCS itself. Dis- implanted as destination therapy with a pulsatile device [73].
advantages to delaying MCS include the high-risk nature of However, the factors associated with higher risk in these studies
transplant during acute illness, further decompensation prior such as signs of RV failure, mechanical ventilation, infection,
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 45: Mechanical Support for Heart Failure 485

TA B L E 4 5 . 3
INTERMACS PROFILES

Profile Description

1 Acutely decompensating
2 Failing inotropes
3 Inotrope dependent, stable
4 Recurrent, but not refractory advanced heart failure
5 Exertion intolerant, but no dyspnea at rest
6 Exertion limited, dyspnea with only mild activity
7 Advanced NYHA class III

NYHA, New York Heart Association.


FIGURE 45.3. Survival after VAD stratified by INTERMACS profile.
1Profile 1; 2Profile 2; 3Profile 3; 4Profile 4. [From Kirklin JK,
Naftel DC, Stevenson LW, et al: INTERMACS database for durable de-
vices for circulatory support: first annual report. J Heart Lung Trans-
plant 27:10651072, 2008, with permission.]
and renal and hepatic dysfunction are also generally seen in
patients who are more ill at the time of implantation.
The Interagency Registry for Mechanically Assisted Circu-
latory Support (INTERMACS) is large national registry of ap- FUTURE DIRECTIONS
proved support devices that was recently established and has
provided a means by which to risk assess patients undergoing Mechanical circulatory support has evolved over the past 25
MCS by their preimplant acuity of illness. INTERMACS has es- years from an investigational strategy reserved only for the
tablished seven different profiles for patients being implanted moribund to a standard therapy supporting patients with stable
with MCS from advanced NYHA class III patients, through advanced heart failure. Today, a wide variety of devices are
inotrope dependence, to acute shock despite maximal medical available for short-term, medium-term, and long-term support
management (Table 45.3) [74]. Data from INTERMACS have at numerous centers worldwide.
shown that risk stratification based solely upon the preimplant A number of newer MCS devices are now in clinical use
profiles does indeed predict outcomes when applied to both or clinical trials. Advances in pump technology are moving to-
pulsatile and continuous flow devices (Fig. 45.3) [33]. There ward smaller pumps that still allow for full support, pumps that
is a substantial difference in survival at 1 year between even can be either implanted percutaneously or through minimally
those who were profiles 1 and 2. A recent study of 101 pa- invasive surgeries, increased durability, totally implantable sys-
tients who received current generation continuous flow devices tems with transcutaneous energy transfer, and an improved
stratified patients based on their preimplant INTERMACS cat- device-patient interface. Research is also focused on improv-
egory: group 1 was profile 1; group 2 was profiles 2 to 3; and ing biocompatibility, lowering risk of thrombosis, and better
group 3 was profiles 4 to 7. Survival at 18 months was 50% responsiveness to physiologic demands.
versus 73% versus 96% ( p < 0.01) for groups 1, 2, and 3 re- The role of MCS as an alternative to transplantation, that
spectively [75]. The implication for patients in the ICU who is, destination therapy, is likely to increase in the future. It is
are stabilized and are being considered for long-term support hoped that with advances in device design, patient selection,
is that there is an emerging consensus that earlier institution and medical management, MCS will be applicable to a greater
of mechanical support is preferable to waiting, as further de- proportion of patients with advanced heart failure, result in
compensation will yield worse outcomes with both MCS and continued improvement in outcomes, and a reduction in ad-
transplantation. verse events and cost.

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Chapter 45: Mechanical Support for Heart Failure 487

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SECTION IV PULMONARY PROBLEMS IN THE


INTENSIVE CARE UNIT
J. MARK MADISON RICHARD S. IRWIN

CHAPTER 46 RESPIRATORY FAILURE PART I:


A PHYSIOLOGIC APPROACH TO
RESPIRATORY FAILURE
THADDEUS C. BARTTER, MELVIN R. PRATTER, WISSAM ABOUZGHEIB AND RICHARD S. IRWIN

nation. For this reason, unlike the physiology of O2 transport,


OVERVIEW lung units with normal or high V/ Q relationships can com-

pensate for areas with low V/Q relationships. Because of these
Respiration serves to oxygenate blood and to remove the
volatile waste product of metabolism, carbon dioxide and re- differences between the two gases, abnormalities in their values
sults in hypoxemia, hypercapnia, or both combined. Although are not always linked, and it is useful to approach the factors
it is traditional to define respiratory failure with abrupt bound- that can cause each to be abnormal.
aries [i.e., arterial carbon dioxide tension (PaCO2 ) greater than
49 mm Hg or arterial oxygen tension (PaO2 ) less than 50 to
60 mm Hg] [1,2], this is too simplistic for the understanding Normal Blood Gas Values
and management of respiratory insufficiency. This chapter dis-
cusses the physiologies leading to the different presentations of Normal PaO2 can be shown to decrease with age and with
respiratory failure and briefly discusses management. the supine position [4]. There is significant standard deviation,
The alveolar PO2 and PCO2 are determined by the relation- and in clinical practice the normal range for most laboratories,
Q
ratio). 80 to 100 mg Hg, suffices.
ship between alveolar ventilation and perfusion (V/
to Q is approximately 0.8 under normal resting In normal human homeostasis, the PaCO2 is tightly regu-
The ratio of V lated by respiration at or close to 40 mm Hg. Unlike the PaO2 ,
conditions. In V/ Q mismatch, the ratio is altered and the ex-
the normal PaCO2 remains at 40 mm Hg throughout life. It is
change of gaseous O2 and CO2 becomes inefficient. There are unaffected by age [4] or position [5].
two V/ Q
mismatch scenarios, termed high V/ Q mismatch The normal pH of human arterial blood is at or close to
and low V/ Q mismatch. High-V/ Q mismatch occurs in a 7.40. Like the PaCO2 , there is no predicted change with age.
lung region that receives a disproportionate increase in venti-
lation or decrease in blood flow. Low V/ Q mismatch occurs
in a lung region that receives a disproportionate decrease in HYPOXEMIA AND HYPERCAPNIA
ventilation or increase in blood flow. As will be seen, low
Q
V/ mismatch plays a major physiologic role in respiratory There are six basic pathophysiologic mechanisms that can lead
failure. to hypoxemia. Some also cause hypercapnia [1,6,7]:
In many cases of respiratory failure, a low PaO2 is coupled 1. Low partial pressure of inspired O2 (PIO2 )
with an elevated PaCO2 , but the physiology of oxygenation 2. Diffusion impairment
is different from that of CO2 removal. The differences stem 3. Right-to-left shunt
in part from the differences in the capacity of blood to carry Q mismatch
4. Low V/
each of the two gases. Oxygen must bind to hemoglobin for
5. Hypoventilation
effective transport. Saturated hemoglobin can carry 1.39 mL
6. High partial pressure of inspired CO2
of O2 per gram, whereas plasma can carry only 0.003 times the
PaO2 ; only approximately 1% of oxygen transport is indepen- Only three are clinically important: low V/ Q
mismatch,
dent of hemoglobin. The amount of O2 that blood can carry is
right-to-left shunt, and hypoventilation. V/Q mismatch and hy-
thus limited by hemoglobin concentration (and function). Once poventilation can cause both hypoxemia and hypercapnia.
hemoglobin is saturated, a doubling of the alveolar oxygen con-
centration has no meaningful impact on oxygen transport. For Low Partial Pressure of Inspired Oxygen
this reason, alveoli with high V/ Q mismatch cannot add extra
oxygen to the pulmonary capillary blood to compensate for Low PIO2 is a potential cause of hypoxemia. A low PIO2 occurs
Q
mismatch in which the hemoglobin of only at high altitudes and in conditions when other gases are
alveoli with low V/
present; it is not in the differential diagnosis of normal clinical
the associated pulmonary capillary blood is not fully saturated
management.
[3].
The biochemistry of CO2 is very different. CO2 diffuses
readily into blood; its quantity increases almost linearly as the Diffusion Impairment
PaCO2 increases. The mechanisms for CO2 transport include It was once thought that thickening of alveolar walls could
a buffering system mediated by carbonic anhydrase and the lead to an increase in the diffusion distance great enough to
formation of carbonyl compounds. The net result is that a prevent equilibrium of the partial pressure of oxygen between
doubling of alveolar ventilation essentially doubles CO2 elimi- the alveoli and the associated pulmonary capillary blood. This

488
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Chapter 46: Respiratory Failure Part I: A Physiologic Approach to Respiratory Failure 489

physiologic concept is known as alveolarcapillary block syn- Q


severe V/ mismatch, there are not enough normal and high
drome, [8]. Subsequent data, however, indicated that even ra- Q
V/ alveoli to compensate for the hypercarbia of those with
diographically homogeneous pulmonary disease rarely alters Q
low V/ mismatch; hypercapnia occurs in addition to hypox-
alveolarcapillary membranes uniformly throughout the lung. emia.
In addition, the efficiency of gas exchange within any single
alveolus is such that even with a barrier to diffusion, diffu-
sion impairment is not a factor; by the time blood leaves the Hypoventilation
alveolar capillaries, alveolar and capillary gas partial pressures Hypoventilation refers to conditions in which minute venti-
are equal. Thus, hypoxemia at rest in patients with patholo- lation is reduced relative to the metabolic demand present for
gies such as interstitial disease is due not to alveolarcapillary oxygen uptake and CO2 production. By necessity, when minute
block but rather to areas of low V/ Q mismatch. In contrast, ventilation is reduced alveolar ventilation must also be abnor-
there may be a component of alveolarcapillary block in ex- mally low, resulting in decreased gas exchange between the
ercise; as the transit time of blood through alveolar capillaries external environment and the alveoli [6]. Hypoventilation by
decreases, there may be some true physiologic impairment of definition causes both arterial hypoxemia and a raised arterial
capillary/alveolar gas equilibrium that could result in hypox- PCO2 . Some physicians use the terms hypoventilation and
emia [9]. carbon dioxide retention interchangeably, a usage that con-
fuses physiologies. Pure hypoventilation represents decreased
Right-to-Left Shunt minute ventilation with normal lungs. In contrast, other condi-
tions that cause carbon dioxide retention (low V/ Q
mismatch)
In right-to-left shunt, blood from the right heart does not come
are caused by airway or parenchymal lung disease and usually
into contact with oxygenated air before reaching the left heart;
are associated with increased minute ventilation.
ventilation and perfusion are uncoupled [5]. Three kinds of
In hypoventilation as defined earlier, the alveolar PCO2 can
shunt are recognized: cardiac, pulmonary vascular, and pul-
rise to the point that the partial pressure of O2 is significantly
monary parenchymal [10]. In a cardiac shunt, a defect allows
reduced. The disorders that cause hypoventilation are called the
blood to pass directly from the right atrium or ventricle into the
extrapulmonary causes of respiratory failure because they do
left-sided chamber. For cardiac shunt to occur, there must be
not involve abnormality of the pulmonary gas exchange mech-
some relative increase in right-sided pressures. In a pulmonary
anisms [7,12,13]. A defect leading to hypoventilation can occur
vascular shunt, the shunting of blood occurs through arteri-
anywhere in the normal physiologic linkages that affect minute
ovenous malformations within the pulmonary vascular bed.
ventilation; the differential diagnosis of extrapulmonary respi-
These arteriovenous malformations can be small and not vis-
ratory failure is listed in Table 46.1. Note that in this catego-
ible on chest imaging (as in some cases of cirrhosis), or large
rization, obstruction at or above the trachea and other large
and visible as parenchymal densities (as with hereditary hemor-
airways is classified as an extrapulmonary disorder because of
rhagic telangiectasia) [11]. In pulmonary parenchymal shunt,
the fact that the gas exchange mechanisms of the lung remain
alveolar consolidation or atelectasis prevents gases from reach-
intact.
ing alveoli while blood flow continues through their capillary
beds. Examples of conditions that cause parenchymal shunt
are pneumonia, lobar collapse, and acute respiratory distress High Partial Pressure of Inspired Carbon Dioxide
syndrome. The inhalation of a gas containing CO2 can cause hypercapnia
Note that right-to-left shunt is listed as a cause of hypox- although it is not usually part of the differential diagnosis in
emia but not of hypercapnia because of the capacity of alveoli clinical medicine. It does occur occasionally in iatrogenic situ-
with normal or high V/ Q
ratios to compensate for the lack
ations; patients on a t-piece with extended tubing attached to
of clearance of CO2 from shunted blood [6]. If the only gas the expiratory port may be forced to re-breathe exhaled CO2
exchange defect present is shunt, increased ventilation to the to the point of hypercapnia.
perfused alveoli leads to a normal PaCO2 [6]. This increased
ventilation has no effect on the PaO2 ; as already noted, the
dependency on hemoglobin for blood to carry oxygen results
in an inability of areas with normal or elevated V/ Q
ratios to TA B L E 4 6 . 1

compensate for areas with low V/Q ratios. Thus, shunt is a DIFFERENTIAL DIAGNOSIS OF EXTRAPULMONARY
cause of nonhypercapnic hypoxemic respiratory failure. RESPIRATORY FAILUREa

Q
V/ Mismatch Site of abnormality Disease

Low V/ Q mismatch is the dominant physiology in abnormal- Central nervous Respiratory center depression owing to
ities of gas exchange. Mild to moderate degrees of low V/ Q
system overdose, primary alveolar
mismatch can cause hypoxemia alone, whereas more severe hypoventilation, myxedema
Q
V/ mismatching leads to hypoxemia with hypercapnia. (For Peripheral nervous Spinal cord disease, amyotrophic
a patient breathing room air, V/ Q mismatch never causes hy- system lateral sclerosis, GuillainBarre
percapnia in the absence of hypoxemia.) There are two reasons syndrome
why a substantially greater amount of low V/ Q
mismatch must Respiratory muscles Muscle fatigue, myasthenia gravis,
be present to cause hypercapnia than to cause hypoxemia. The polymyositis, hypophosphatemia
first reason is the higher solubility of CO2 in blood as discussed Chest wall Ankylosing spondylitis, flail chest,
earlier [6]; there is no saturation limit for CO2 . Thus while nor- thoracoplasty
mal alveoli cannot increase oxygen uptake significantly after Pleura Restrictive pleuritis
hemoglobin saturation, they can increase CO2 removal as ve- Upper airway Tracheal stenosis, vocal cord tumor
nous CO2 content rises. The second reason is that, just as with obstruction
shunt, patients with low V/ Q mismatch increase their minute a
This table is not an exhaustive listing; it includes the more common
ventilation to compensate for the potential elevation in CO2 causes for each involved compartment of the respiratory system.
that the low V/ Q areas would otherwise generate [6]. With
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490 Section IV: Pulmonary Problems in the Intensive Care Unit

Overlapping Factors a steady state, R can be assumed to be 0.8, even in patients with
significant lung disease [18]. Given the previous assumptions
Several comments are in order. First, more than one mecha-
and a normal PaCO2 of 40 mm Hg, one gets an idealized PAO2
nism may be operant in any individual case. For example, a
of 100:
high ventilatory requirement needed to compensate for areas
Q
of low V/ mismatch in a patient with chronic obstructive pul- PAO2 = 150 40/0.8 = 100
monary disease may lead to muscle overload with fatigue and The Aa gradient is then obtained by subtracting the mea-
therefore add an extrapulmonary etiology of hypercapnia to sured arterial PO2 from the calculated PAO2 . PCO2 /0.8 is the
primary pulmonary disease. Another common coupling would same as the PCO2 1.25. Thus, for a person breathing room
be the coexistence of V/ Q
mismatch and pulmonary parenchy-
air at sea level,
mal shunt in a patient with pneumonia and underlying chronic
obstructive pulmonary disease (COPD). Aa gradient is equal to = 150 (1.25 PaCO2 ) PaO2
Second, a decrease in cardiac output may worsen hypox- In reality, the lung is not a single large alveolus, and there is
emia primarily due to marked V/ Q abnormalities, a large right- not an oxygen gradient between the alveolus and the capillary.
to-left shunt, or both. A decrease in cardiac output forces a The calculated gradient represents a mixture of blood from
compensatory increase in oxygen extraction at the tissue level, alveoli with ideal characteristics with blood from alveoli that
leading to a decreased mixed-venous oxygen content. Isolated have low V/ Q mismatch and with shunted blood. The greater
reduction in the mixed-venous oxygen content is not a cause the contribution from alveoli with low V/ Q mismatch and from
of hypoxemia, but it can exacerbate the hypoxemia generated shunt, the greater the Aa gradient.
by any of the primary mechanisms described above. One value of the concept of the Aa gradient is that it can be
Third, as mentioned, shunt alone is not a cause of hyper- used to separate the extrapulmonary causes of respiratory fail-
capnia, but if a significant shunt is present in conjunction with ure from those that involve parenchymal lung disease [12] as
one of the primary causes of hypercapnia, then the capacity to long as the patient is breathing room air. With extrapulmonary
compensate for the shunt is reduced and hypercapnia is wors- failure, the Aa gradient remains normal. With shunt or V/ Q
ened. Q mismatch and
mismatch, the gradient is usually elevated. V/
Finally, the PaCO2 represents a balance between CO2 pro-
extrapulmonary respiratory failure are the two causes of hy-
duction and CO2 clearance; in patients with an impaired ca-
percapnia encountered in clinical practice, and the Aa gradi-
pacity to clear CO2 , increases in production may gain clinical
ent is a useful tool for distinguishing between them. Gray and
relevance [14]. Fever increases CO2 production by 13% for
Blalock have noted that the Aa gradient is an imperfect tool;
each 1 C temperature elevation above normal. Thus, lowering
with very high PaCO2 , the gradient can narrow [19]. This is
temperature to normal may have an impact on PaCO2 in a
Q mismatch. Nutri- rarely an issue in clinical management. At any age, an Aa gra-
febrile patient with a large amount of V/ dient exceeding 20 mm Hg on room air should be considered
tional support with excessive total calories or proportionally abnormal and indicative of pulmonary dysfunction [16].
high-carbohydrate loads also increases CO2 production [15]. When the FIO2 is above 0.21, the Aa gradient becomes
It follows that decreasing total caloric load may influence the a less accurate measure of the efficiency of gas exchange and
degree of hypercapnia in patients with limited ventilatory re- therefore a less valuable tool for the measurement of shunt,
serve. Q
V/ mismatch, or the lack thereof. The PaO2 divided by the
FIO2 (PaO2 /FIO2 ratio) can be used to assess the severity of the
gas exchange defect. For calculation, the FIO2 is expressed as
ANALYTICAL TOOLS FOR a decimal ranging from 0.21 to 1.00. The normal PaO2 /FIO2
HYPOXEMIA AND HYPERCAPNIA is 300 to 500. A value of <300 is indicative of gas exchange
derangement and a value below 200 is indicative of severe im-
Several tools can be used to categorize type and severity of the pairment. Although the PaO2 /FIO2 is felt to be a more reliable
different causes of hypercapnia and hypoxemia. Simple cal- measure of degree of gas exchange impairment at higher FIO2 s,
culation, maneuvers, and tests can give the clinician a better it too has the potential to be unreliable, particularly in the pres-
understanding of the underlying physiology. ence of a large shunt or a low FIO2 [2022].

Calculation of AlveolarArterial PO2 100% Oxygen Inhalation Challenge


Gradient and PaO2 /FIO2 Ratio A trial of 100% oxygen inhalation can be used to separate low
The Aa PO2 gradient, although a conceptual simplification, is Q
V/ mismatch from shunt as the cause of respiratory failure. In
clinically useful. It allows separation of extrapulmonary from areas of low V/ Q
mismatch, the alveolar PO2 is low. If 100%
pulmonary causes of respiratory failure [16,17]. It presents a oxygen is delivered via a closed system, even a poorly ventilated
mathematical model as though the lung were one large alveo- alveolus in theory soon contains 100% oxygen diluted only by
lus and the entire blood flow of the right heart passed around the partial pressures of water and CO2 [1]. Thus, with low V/ Q
that alveolus. Rules of partial pressure and the respiratory ex- mismatch, the PaO2 rises dramatically if the FIO2 is increased.
change ratio, R, are used to calculate the theoretical alveolar In contrast, areas of shunt are never exposed to O2 , and there
PO2 (PAO2 ). The PIO2 is reduced first by water pressure in the is no response to an increase in FIO2 . If the PaO2 with the
airways and then at the alveolar level by the alveolar PaCO2 . patient breathing 100% O2 is greater than 500 mm Hg, then
Exchange of oxygen and CO2 at the alveolar level is reflected Q
mismatch [1]. If the PO2
prior hypoxemia is largely due to V/
in the respiratory exchange ratio, R. This is the basis for the
on 100% O2 is less than 350 mm Hg, then major shunting is
alveolar air equation [18],
present.
PAO2 = PIO2 PaCO2 /R
Ambient air at sea level has a total pressure of 760 mm Hg,
Nuclear Scanning and Echocardiography
21% of which is oxygen. As air is inhaled it is humidified by Nuclear scanning and echocardiography can be used to deter-
water vapor, which has a partial pressure of approximately 47 mine the etiology of a shunt. As previously stated, a right-to-
at normal body temperature. The partial pressure of O2 after left shunt can be pulmonary parenchymal, pulmonary vascular,
inhaled air is humidified is therefore 0.21 (760 47), or 150. In or intracardiac. Nuclear perfusion scanning for evaluation of
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Chapter 46: Respiratory Failure Part I: A Physiologic Approach to Respiratory Failure 491

shunt takes advantage of the fact that the technetium-labeled TA B L E 4 6 . 2


macroaggregated albumin used for the scan is a relatively large
particle that does not pass through capillaries. This charac- THE DIFFERENTIAL DIAGNOSIS OF HYPERCAPNIA
teristic can help to separate shunt with normal vasculature
from shunt due to abnormal vascular connections. If vascu- Hypercapnia with elevated Hypercapnia with normal
lar anatomy is normal (and shunt is produced by blood flow Aa gradient Aa gradient
through normal capillaries traversing consolidated lung), the
Q
Low V/ mismatch Extrapulmonary respiratory
technetium-labeled molecules of the nuclear scan are filtered
by the pulmonary capillaries and remain in the lung. In con- COPD failure (see Table 46.1)
trast, with abnormal connection(s) between the right and left Obesity/hypoventilation
heart vasculatures, significant amounts of technetium-labeled syndrome
particles bypass pulmonary capillaries and are then filtered by Rebreathing CO2
systemic capillaries (e.g. brain and kidneys). Thus, a nuclear
scan obtained to classify and quantify shunt shows immedi-
ate renal and cerebral uptake if the shunt is cardiac or pul-
monary vascular and only pulmonary uptake if the shunt is H+ /PCO2 Ratio
of pulmonary parenchymal origin [10]. If the shunt is not pul-
monary parenchymal, the final step to differentiate intracardiac Ability to calculate the H+ concentration allows calculation of
from pulmonary parenchymal is contrast echocardiography. the H+ /PCO2 ratio that is of value in understanding respi-
Contrast echocardiography can document right-to-left cardiac ratory acid-base disorders. The H+ /PCO2 is calculated as
shunting if present [17,23,24]; immediate transit (within four the change in H+ from baseline (baseline assumed usually to be
cardiac cycles) to the left heart can be seen with intracardiac 40 nanoequivalents per liter that corresponds to a pH of 7.40)
shunt. If there is no cardiac shunt or if contrast appears after divided by the change in PaCO2 from baseline (baseline again
five cardiac cycles, then the abnormal vascular connection is in 40). For example, for the theoretical blood gas (pH, PaCO2 ,
the pulmonary circulation. PaO2 ), 7.32/50/60, the change in PCO2 is 10 and the change
in H+ concentration is 8 (48 40); the ratio is therefore 0.8.
An acute change of PCO2 in either direction causes an im-
RESPIRATORY ACIDBASE mediate and predictable change in H+ and thus a predictable
H+ /PCO2 [25,26]. If a respiratory alteration persists, how-
DISORDERS ever, renal mechanisms increase or decrease serum HCO3 in a
Acidbase analysis can be used to understand the nature and direction that pushes the H+ back toward normal; maintenance
acuity of a respiratory disturbance, both essential for clinical of H+ homeostasis is a primal physiologic function. Thus, after
management. Relationships between PaCO2 , pH, and bicar- renal compensation occurs, the H+ /PCO2 ratio is altered.
bonate concentration (HCO3 ) can be used first to determine This alteration represents the chronic state.
whether there is a primary respiratory or metabolic process,
whether it is simple (one acidbase disturbance) or complicated
(more than one), and whether it is acute or chronic [25]. A res- Respiratory Acidosis/Respiratory Alkalosis
piratory disturbance is defined by a primary change in PaCO2 ,
whereas a metabolic disorder involves a primary change in the Respiratory acidosis is defined as an acidosis associated with
HCO3 (see Chapter 72). An acute process is one occurring in and caused by an elevation of the PaCO2 . By definition there-
minutes to hours, whereas a chronic process has persisted for fore, respiratory acidosis is a product of hypercapnia (See
several days or longer. This chapter concentrates on acute and Table 46.2). Knowledge of the H+ concentration in addition to
chronic simple respiratory disorders. the PaCO2 , however, allows for calculation of the H+ /PCO2
Acidbase balance is assessed clinically from the arterial hy- ratio. A ratio of 0.8 (as in the earlier example) implies an
drogen ion (H+ ) concentration and may be expressed either in acute respiratory acidosis [26]. A ratio of 0.3 implies a chronic
nanoequivalents per liter or as the negative logarithm of that (and compensated) respiratory acidosis [26]. Values for the
number, pHa . H+ concentration can be assessed with knowl- H+ /PCO2 ratio between 0.3 and 0.8 correspond to an
edge of the concentration of any of many potential hydrogen acute-on-chronic respiratory acidosis (as often occurs with an
donors and the dissociation constant for that donor. The mass exacerbation of chronic obstructive pulmonary disease) [26].
action equation that demonstrates the capacity of CO2 to act as Respiratory alkalosis is defined as an alkalosis caused by
an acid (CO2 + H2 O H2 CO3 H+ + HCO3 ), is of clinical a decrease in PaCO2 that drives the CO2 in the mass action
relevance and also convenient, given that PaCO2 and HCO3 equation to the left: H+ and HCO3 concentrations decrease.
are easily measured. An increase in CO2 drives the equation to The differential diagnosis for respiratory alkalosis is listed in
the right, increasing H+ concentration. An increase in HCO3 Table 46.3. When the H+ /PCO2 ratio is used to analyze
drives the equation to the left, decreasing the H+ concentra- a pure respiratory alkalosis, a ratio of 0.8 corresponds to an
tion. The Henderson version of the HendersonHasselbalch acute respiratory alkalosis and a ratio of 0.17 corresponds to
equation [3], H+ = 24 (PaCO2 /HCO3 ), calculates actual H+ a chronic respiratory alkalosis [26].
concentration using those measurements. Clinically, all acid
base disorders can be evaluated using this basic equation [4].
CLINICAL APPROACH TO
RESPIRATORY FAILURE
Calculation of H+ Concentration
Respiratory failure occurs when gas exchange becomes signif-
In clinical practice, the pH is the value reported, but knowledge icantly impaired. It is impossible to accurately predict PaO2
of the H+ concentration can often facilitate the diagnosis of and PaCO2 using clinical criteria [27,28]; the diagnosis of res-
respiratory acidbase disturbances. The relationship between piratory failure depends on arterial blood gas (ABG) analysis.
H+ and pH and how to predict H+ from pH, essential to the Various clinical signs and symptoms, including those reflect-
following discussion, is covered in Chapter 11. ing the effects of hypoxemia or hypercapnia, or both, on the
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492 Section IV: Pulmonary Problems in the Intensive Care Unit

TA B L E 4 6 . 3
Scenario 3
CAUSES OF RESPIRATORY ALKALOSISa
The patient arrives with a PaO2 of 42, PaCO2 of 68, and pH
Elevated Aa gradient Normal Aa gradient of 7.21. Calculation of the Aa gradient yields a value of 23.
You administer naloxone and the patient does awaken, but he
Sepsis and capillary leak Central nervous system disorder remains hypoxemic. This was anticipated owing to the elevated
syndrome Hepatic failure with normal lungs Aa gradient; you evaluate for an additional process such as
Hepatic failure with Analeptic overdose drugs aspiration of gastric contents.
hepatopulmonary Salicylates In an acute-on-chronic situation, the trend of the acidosis is
syndrome Catecholamines most crucial in deciding whether mechanical ventilatory sup-
Chronic interstitial lung Progesterone port is necessary [7]. Although these ratios are strictly correct
diseases Thyroid hormone excess only for simple respiratory acidbase disturbances, the authors
Pulmonary edema Pregnancy believe they should be applied therapeutically even in a compli-
Cardiogenic High altitude cated disturbance. If the ratio is consistent with an acute respi-
Noncardiogenic (acute Severe anemia (approximately ratory acidosis, the patient who fails to improve with treatment
respiratory distress 3 g/dL hemoglobin) should receive ventilatory support (see Chapters 58, 59).
syndrome) Psychogenic hyperventilation Fear of causing greater hypercapnia should not be a deter-
Pulmonary embolism Endotoxemia rent to the use of supplemental oxygen in an acutely ill hy-
Pneumonia Mechanical hyperventilation with poxemic patient. Although PaCO2 predictably increases with
Asthma normal lungs the use of supplemental oxygen in patients with hypercapnia
Right-to-left shunt During menses after ovulation Q
due to V/ mismatch, CO2 narcosis is very uncommon. It does,
however, make sense to start supplemental oxygen at a low con-
P(Aa)O2 , alveolararterial oxygen tension gradient. centration and then to slowly increase the FIO2 until adequate
a
The differential diagnosis of respiratory alkalosis with an elevated oxygenation is achieved. The uncommon case of resultant se-
P(Aa)O2 gradient is the same as that of nonhypercapnic, hypoxemic
vere hypercapnia can be treated with mechanical ventilatory
respiratory failure.
support.
Respiratory alkalosis is not itself a cause of respiratory fail-
ure unless the increased work of breathing cannot be sustained
by the respiratory muscles. Management therefore depends on
central nervous system and cardiovascular system, may lead to diagnosis of the underlying stimulus for hyperventilation and
suspicion of the diagnosis, but the ABG must be obtained for on treatment specific to that condition (e.g., heparin for pul-
confirmation. A clinical approach to respiratory failure begins monary embolism). When respiratory alkalosis continues to
with analysis of the ABG for the severity, type, and acuity of worsen in critically ill patients on mechanical ventilatory sup-
the gas exchange disturbance. These factors and the expected port, however, it may become necessary to treat the respiratory
duration of the process guide interventions. alkalosis directly. In such a setting, sedation with or without
Acute hypercapnia should be evaluated for reversible paralysis of skeletal muscles can be useful.
causes. If none is found, mechanical ventilatory support, inva- Hypoxemia that responds only minimally to large increases
sive or noninvasive, is needed. This can take the form of intuba- in FIO2 involves significant shunt. (In many clinical situations,
tion, but other options such as continuous positive airway pres- such as chronic obstructive pulmonary disease with pneumo-
sure and noninvasive positive-pressure ventilation now have a nia, the physiology involves a coupling of shunt and V/ Q
documented role in the management of acute respiratory com- mismatch.) Cardiac shunt or large pulmonary arteriovenous
promise [29]. Hypercapnia with a H+ /PCO2 ratio of 0.3, shunts may require an invasive intervention to correct them.
indicating chronicity, uncommonly requires urgent ventilatory Diffuse pulmonary parenchymal shunt, as can occur in acute
support. respiratory distress syndrome, may be amenable to positive
end-expiratory pressure.
Noninvasive ventilation has been studied extensively. In
CLINICAL EXAMPLES clinical scenarios in which reversal or amelioration of the un-
derlying process may be possible within the short term, nonin-
vasive ventilation may provide a therapeutic bridge that allows
Scenario 1 avoidance of the possible disadvantages of intubation and me-
chanical ventilation [29].
A 29-year-old man is brought to the emergency department in a
stuporous state. ABGs drawn on room air at the time of arrival
demonstrate a PaO2 of 52, PaCO2 of 68, and pH of 7.21. On
calculation, the Aa gradient is 13 and the H+ /PCO2 ratio
CONCLUSION
is 0.8. You therefore know that you are dealing with an acute The basic physiologic mechanisms underlying all abnormali-
respiratory acidosis of extrapulmonary origin. The narcotic an- ties of gas exchange have been delineated. Of these, the most
tagonist naloxone is administered, and the patient wakes up, Q mismatch, hypoventilation, and
clinically relevant are low V/
with normalization of blood gases.
shunt. A series of tools that can be used to analyze and differ-
entiate these physiologic possibilities has been presented along
with an analysis of how H+ /PaCO2 relationships can help to
Scenario 2 define the acuity of a disorder. Analysis of the type and acuity
of a process should lead to an attempt to define the responsible
The same patient, given naloxone and flumazenil, has no disease process(es) and to intervene specifically. The decision of
change in blood gases or mental status. Your differential di- when or whether to institute mechanical ventilatory support,
agnosis is now acute extrapulmonary respiratory failure other especially with intubation, is not always clear from numbers
than narcotic or benzodiazepine respiratory suppression. You alone; this decision involves the art as well as the science of
intubate and start mechanical ventilation. medicine.
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Chapter 47: Respiratory Failure Part II: Acute Respiratory Distress Syndrome 493

References
1. West JB: Pulmonary Pathophysiology: The Essentials. Baltimore, Williams 17. Chen WJ, Kuan P, Lien WP, et al: Detection of patent foramen ovale by
& Wilkins, 1982. contrast transesophageal echocardiography. Chest 101:1515, 1992.
2. Pontoppidan H, Geffin B, Lowenstein E: Acute respiratory failure in the 18. Begin R, Renzetti AO Jr: Alveolar-arterial oxygen pressure gradient. I. Com-
adult. 1. N Engl J Med 287:690, 1972. parison between and assumed and actual respiratory quotient in stable
3. Murray JF: The Normal Lung: The Basis for Diagnosis and Treatment of chronic pulmonary disease. II. Relationship to aging and closing volume
Pulmonary Disease. Philadelphia, PA, WB Saunders, 1976. in normal subjects. Respir Care 22:491, 1977.
4. Cerveri I, Zoia MC, Fanfulla F, et al: Reference values of arterial oxygen 19. Gray BA, Blalock JM: Interpretation of the alveolar-arterial oxygen differ-
tension in the middle-aged and elderly. Am J Respir Crit Care Med 152:934, ence in patients with hypercapnia. Am Rev Respir Dis 143:4, 1991.
1995. 20. Bernard GR, Artigas A, Brigham KL, et al: The American-European Con-
5. Bates DV: Respiratory Function in Disease. Toronto, WB Saunders, 1989. sensus Conference on ARDS. Definitions, mechanisms, relevant outcomes,
6. West JB: Causes of carbon dioxide retention in lung disease. N Engl J Med and clinical trial coordination. Am J Respir Crit Care Med 149:818,
284:1232, 1971. 1994.
7. Demers RR, Irwin RS: Management of hypercapnic respiratory failure: a 21. Whiteley JP, Gavaghan DJ, Hahn CE: Variation of venous admixture, SF6
systematic approach. Respir Care 24:328, 1979. shunt, PaO2 , and the PaO2 /FIO2 ratio with FIO2 . Br J Anaesth 88:771,
8. Finley TN, Swenson EW, Comroe JH Jr: The cause of arterial hypoxemia 2002.
at rest in patients with alveolar capillary block syndrome. J Clin Invest 22. Gowda MS, Klocke RA: Variability of indices of hypoxemia in adult respi-
41:618, 1962. ratory distress syndrome. Crit Care Med 25:41, 1997.
9. Murray JF: Pathophysiology of acute respiratory failure. Respir Care 28:531, 23. Cox D, Taylor J, Nanda NC: Refractory hypoxemia in right ventricu-
1983. lar infarction from right-to-left shunting via a patent foramen ovale: ef-
10. Robin ED, Laman PD, Goris ML, et al: A shunt is (not) a shunt is (not) a ficacy of contrast transesophageal echocardiography. Am J Med 91:653,
shunt. Am Rev Respir Dis 115:553, 1977. 1991.
11. Bartter T, Irwin RS, Nash G: Aneurysms of the pulmonary arteries. Chest 24. Suzuki Y, Kambara H, Kadota K, et al: Detection of intracardiac shunt
94:1065, 1988. flow in atrial septal defect using a real-time two-dimensional color-coded
12. Pratter MR, Irwin RS: Extrapulmonary causes of respiratory failure. J Int Doppler flow imaging system and comparison with contrast two-dimensional
Care Med 1:197, 1986. echocardiography. Am J Cardiol 56:347, 1985.
13. Pratter MR, Corwin RW, Irwin RS: An integrated analysis of lung and res- 25. Narins RG, Emmett M: Simple and mixed acid-base disorders: a practical
piratory muscle dysfunction in the pathogenesis of hypercapnic respiratory approach. Medicine (Baltimore) 59:161, 1980.
failure. Respir Care 27:55, 1982. 26. Bear RA, Gribik M: Assessing acid-base imbalances through laboratory pa-
14. Weinberger SE, Schwartzstein RM, Weiss JW: Hypercapnia. N Engl J Med rameters. Hosp Practice 157, 1974.
321:1223, 1989. 27. Mithoefer JC, Bossman OG, Thibeault DW, et al: The clinical estimation of
15. Talpers SS, Romberger DJ, Bunce SB, et al: Nutritionally associated increased alveolar ventilation. Am Rev Respir Dis 98:868, 1968.
carbon dioxide production. Excess total calories vs high proportion of car- 28. Comroe JH Jr, Botelho S: The unreliability of cyanosis in the recognition of
bohydrate calories. Chest 102:551, 1992. arterial anoxemia. Am J Med Sci 214:1, 1947.
16. Mellemgaard K: The alveolar-arterial oxygen difference: its size and compo- 29. Mehta S, Hill NS: Noninvasive ventilation. Am J Respir Crit Care Med
nents in normal man. Acta Physiol Scand 67:10, 1966. 163:540, 2001.

CHAPTER 47 RESPIRATORY FAILURE


PART II: ACUTE RESPIRATORY DISTRESS
SYNDROME
GILMAN B. ALLEN AND POLLY E. PARSONS

unit [7,8]. Fortunately, an enormous body of research already


INTRODUCTION exists on the pathogenesis of this condition, and advances con-
tinue to develop with regard to our understanding of ALI, its
Acute lung injury (ALI) and the acute respiratory distress syn- prognostic implications, and how to best manage the condition
drome (ARDS) represent a continuum of severity for the same medically.
pathologic condition, both being defined by noncardiogenic
pulmonary edema and hypoxemia in the setting of direct or
indirect lung injury. Because ARDS, by definition, simply rep-
resents a more severely advanced form of ALI, the term ALI DEFINITION
can be used as a comprehensive term for both conditions. ALI
represents a common pathologic endpoint of various potential ALI is defined as a diminished arterial oxygen pressure (PaO2 )
insults to the lung that almost invariably lead to hypoxemic res- to fractional inspired oxygen (FiO2 ) ratio (P to F (P:F) ratio
piratory failure requiring support with mechanical ventilation. less than 300), bilateral airspace disease on chest radiograph,
Despite the confirmed success of protective mechanical ventila- and pulmonary edema from increased permeability, the latter
tion strategies in lowering mortality [1,2] and ongoing efforts defined by evidence of normal cardiac function [9]. ARDS is
to discover other effective interventions [36], treatment of this simply a subset of ALI having a more severely diminished P:F
condition remains largely supportive, and ALI continues to be ratio (less than 200). However, because the P:F ratio can be af-
a major source of morbidity and mortality in the intensive care fected by arbitrary ventilator settings [10], and because many
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494 Section IV: Pulmonary Problems in the Intensive Care Unit

TA B L E 4 7 . 1
RECOMMENDED CRITERIA FOR ACUTE LUNG INJURY (ALI) AND ACUTE RESPIRATORY DISTRESS
SYNDROME (ARDS)

Timing Oxygenation Chest radiograph Pulmonary artery wedge pressure

ALI Criteria Acute onest PaO2 /FiO2 300 mm Hg Bilateral infiltrates seen on 18 mm Hg when measured OR no
(regardless of PEEP) frontal chest radiograph clinical evidence of left atrial
hypertension
ARDS Criteria Acute onset PaO2 /FiO2 200 mm Hg Bilateral infiltrates seen on 18 mm Hg when measured OR no
(regardless of PEEP) frontal chest radiograph clinical evidence of left atrial
hypertension

From Bernard GR, Artigas A, Brigham KL, et al: The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant
outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149:818824, 1994.

studies have shown that indices of oxygenation are not strongly been well characterized and is, in many ways, descriptive of its
predictive of outcome [1113], this differentiation may be of pathogenesis.
limited clinical relevance. Furthermore, the definition of ALI
and ARDS has undergone significant evolution over the years,
and limitations of this definition still exist [14], which can HISTOPATHOLOGY
confound the interpretation of older research results and con-
tribute added challenges to the design of new studies. Despite having many different potential etiologies [1618],
In response to the recognized limitations in determining the the histologic findings of ALI are fundamentally uniform and
incidence and outcomes of ALI, a committee of leading investi- are collectively described by the term, diffuse alveolar dam-
gators in the field met in 1994 to develop a consensus between age (DAD) [19]. DAD represents a continuum of changes that
the American Thoracic Society and the European Society of can be temporally divided into exudative, proliferative, and
Intensive Care Medicine. The most current definition of ALI fibrotic phases [19,20], between which considerable overlap
derives from this consensus [9] and defines the condition as exists. The exudative phase of DAD is the earliest phase, dur-
the acute onset of hypoxemia and noncardiogenic pulmonary ing which clinical symptoms first develop and lung mechanical
edema (see Table 47.1). Although the source of hypoxemia in changes become manifest [21]. This phase typically occupies
ALI is multifactorial, it is one of the most easily gauged markers the first week and is characterized by epithelial and endothelial
of lung injury in the intensive care unit and thus an impor- cell death, neutrophil sequestration, plateletfibrin thrombi,
tant component of the definition. Despite its limited prognostic interstitial edema, and exudates within the airspaces, which
value, the more inclusive P:F ratio of less than 300 can serve consist of fluid, protein, and cellular debris [19]. These exu-
to identify patients earlier in their course [11], thus expediting dates compact into dense, protein-rich hyaline membranes that
delivery of critical life saving interventions before progression stain strongly with eosin and line the alveoli and alveolar ducts
to ARDS. In ALI, the pulmonary edema is the result of capil- (Fig. 47.1A). During the second week of injury, the prolifer-
lary leak, a parameter that is difficult to measure in the clin- ative phase ensues, which is characterized by organization of
ical setting. Accordingly, noncardiogenic pulmonary edema is the intra-alveolar exudates and proliferation of type II alveolar
defined using clinical parameters, which include the presence cells, fibroblasts, and myofibroblasts. During this phase, it is
of bilateral infiltrates consistent with pulmonary edema on common to find areas of squamous metaplasia and granulation
chest radiograph and either a pulmonary artery wedge pressure tissue occluding alveolar ducts in a manner similar to that of
(PAWP) less than 18 mm Hg (when measured) or no clinical organizing pneumonia (Fig. 47.1B) [22].
evidence of left atrial hypertension [9]. However, because the The fibrotic phase has classically been considered the later
group recognized that ALI does not always exist exclusively phase of remodeling that occurs in patients who survive past
without heart failure, the consensus more explicitly defines ALI 3 or 4 weeks [19]. However, studies suggest an increase in
as a syndrome of inflammation and increased permeability the fibrotic response to ALI as early as 24 hours from pre-
that is associated with a constellation of clinical, radiologic, sentation [23], and histologic evidence can be seen within the
and physiologic abnormalities that cannot be explained by, but first 2 weeks of diagnosis [24]. Because such overlap exists be-
may coexist with, left atrial or pulmonary capillary hyperten- tween the fibrotic and proliferative phases, the two are often
sion[9]. described together as the fibroproliferative phase. On histology,
Despite the great lengths taken to clarify the current defini- alveolar septa are expanded and airspaces filled with sparsely
tion of ALI, it is not without its shortcomings, particularly be- cellular connective tissue [19]. Such airspace connective tissue
cause it does not delineate the cause of hypoxemia (i.e., alveolar formation can either resolve or progress to the point of com-
damage) or clearly establish the presence of increased perme- plete airspace obliteration [24], fibrosis, and even honeycomb-
ability [14]. Unfortunately, easily employed tests for microvas- ing [22]. Regardless of severity, there is evidence that increased
cular permeability are not yet available, and what degree of fibroproliferative signaling [23] and fibrosis [24] predict worse
permeability is needed to reliably predict the presence of alve- outcomes.
olar damage is not known [14]. The boundaries for the P:F
ratio are also arbitrary. The consensus committee recognized
the difficulty in interpreting this ratio in the setting of differ- RADIOGRAPHIC FINDINGS
ent levels of positive end-expiratory pressure (PEEP) [15], and
thus decided to not include this parameter in their definition. The diagnostic criteria of ALI require bilateral infiltrates on
It would also be impractical to base the clinical definition of frontal chest radiograph [9]. These infiltrates will often ini-
ALI upon histologic findings given the often critical condition tially appear as heterogeneous opacities, but later become more
of patients and their poor candidacy for biopsy by the time of homogenous over hours to days [25] (see Fig. 47.2A). Al-
clinical diagnosis. Nevertheless, the histopathology of ALI has though some have recommended using criteria such as cardiac
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Chapter 47: Respiratory Failure Part II: Acute Respiratory Distress Syndrome 495

FIGURE 47.1. A: Histologic lung spec-


imen from ARDS patient, showing
red blood cells and neutrophils within
the alveolar space and characteris-
tic hyaline membranes (arrow) consis-
tent with diagnosis of diffuse alveolar
damage (DAD). B: Hematoxylin and
eosin stained, 60; demonstrates distal
airspace granulation tissue (asterisks)
consistent with organizing pneumonia.
A B [Images were graciously provided by Dr.
Martha Warnock.]

silhouette size and vascular pedicle width to differentiate car- involvement, all of which contribute to low interobserver
diogenic from noncardiogenic edema, this differentiation has agreement [27].
proven difficult [26]. Furthermore, the seemingly straightfor- Prior to computed tomography (CT) scanning, the pul-
ward interpretation of bilateral infiltrates can be obscured by monary edema seen on chest radiograph was widely believed to
factors such as atelectasis, effusions, or isolated lower lobe be a diffuse process. However, CT imaging has demonstrated

FIGURE 47.2. A plain chest radiograph from a patient with


ARDS [generously provided by Dr. Jeff Klein]. B, C: Com-
puted tomography images of the chest from patients with
ARDS [Images reproduced with permission from Good-
man LR, Fumagalli R, Tagliabue P, et al: Adult respiratory
distress syndrome due to pulmonary and extrapulmonary
causes: CT, clinical, and functional correlations. Radiology
213:545552, 1999.]. B: Diffuse patchy regions of consoli-
dation with a predominance of ground glass infiltrates and
small effusion (arrow). C: A predominance dense consoli-
C dation (arrow), particularly at the bases, with sparse areas
of ground glass.
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496 Section IV: Pulmonary Problems in the Intensive Care Unit

the distribution of ALI to oftentimes be heterogeneous and tiation is justified by the demonstration of differing physiologic
patchy, with areas of normal-appearing, aerated lung inter- properties between ALI of a direct or indirect nature [38], and
spersed among areas of mixed ground glass opacity and con- by the varied outcomes associated with different causes of ALI
solidation, the latter being concentrated in the more gravita- [7,11,13]. It is now well established that sepsis is the most com-
tionally dependent regions of the lung [28] (see Fig. 47.2B, C). monly identified cause of ALI, and is associated with the worst
Despite this pattern, a recent study using positron emission outcome overall [7,13,18], while trauma-related ALI has a sig-
tomography (PET) to map cellular metabolic activity demon- nificantly lower mortality [7]. These differences in mortality
strated that diffuse inflammatory change can be detected even may be in part due to differences in pathogenesis [39]. Other
in areas of the lung that appear spared radiographically [29]. risk factors for the development of ALI following a known in-
Some investigators have also used PET imaging and magnetic sult include a history of alcoholism [4042], recent chemother-
resonance imaging (MRI) to estimate pulmonary microvascular apy [41], delayed resuscitation [41], and transfusion with blood
leak and assist in the differentiation between high permeability products [4346]. The latter condition, commonly referred to
and hydrostatic pulmonary edema [3032], but these methods as transfusion-related ALI (i.e., TRALI), may be more likely
have yet to be adopted in clinical practice. to develop following transfusion with fresh frozen plasma and
platelets than with packed red blood cells (PRBCs) [44]. Curi-
ously, in those at clinical risk for developing ALI, the diagnosis
EPIDEMIOLOGY of diabetes mellitus has been shown to confer protection from
ALI, providing about half the relative risk as that of nondia-
The estimated incidence of ALI worldwide has been variable in betic patients [41,47].
the past due to its wide range of causes and previously nonuni-
form definition. The first estimate by the National Institutes
of Health (NIH) projected an annual incidence of 75 cases PATHOGENESIS
per 100,000 in the United States [33]. Two subsequent cohort
studies in Scandinavia and Australia, respectively, estimated an An understanding of the pathogenesis of ALI is perhaps best
annual incidence of 18 and 34 cases per 100,000 [34,35], but imparted through a reflection on the predominant pathologic
these studies were limited in size and case inclusion. A much findings on histology. First and foremost, ALI is a condition
lager pool of prospective cases from the NHLBI-sponsored triggered by injury to the alveolar epithelium and capillary en-
ARDS Network yielded a conservative estimate of 64.2 cases dothelium. The insult can be initially isolated to either the ep-
per 100,000 person-years [36]. A more recent and significantly ithelium, as in the case of aspiration, or to the endothelium, as
larger prospective cohort study from King County in Wash- in most forms of indirect ALI such as sepsis. However, injury is
ington State estimates an annual incidence of 78.9 cases per generally detected in both the endothelium and epithelium by
100,000 person-years [7], which is more in accordance with the time of diagnosis [19,48]. This injury invariably leads to
the ARDS Network and original NIH estimates, and is likely a leakage of plasma proteins into the alveolar space. Many of
to be the most accurate estimate to date for incidence in the these plasma proteins in turn activate procoagulant and proin-
United States. flammatory pathways that lead to the fibrinous and purulent
In patients at risk of developing ALI, the onset of ALI is exudates seen on histology. Through increased transcription
typically swift, with a median duration of 1 day (interquartile and release of proinflammatory cytokines, and an increased ex-
range 0 to 4 days) from the time of risk factor development to pression of cell surface adhesion molecules, a profound acute
the time of diagnosis [37]. The known causes and risk factors inflammatory response ensues. This is heralded by epithelial
for the development of ALI have been well characterized [16 cell apoptosis and necrosis [49], further activation of inflam-
18] (see Table 47.2), and can be categorized as ensuing from matory cascades, and a robust recruitment of neutrophils [50].
either direct or indirect injury to the lung [16,38]. This differen- The increased expression of tissue factor and other procoag-
ulant factors ultimately leads to coagulation within the mi-
crovasculature and airspaces, accompanied by a suppression
TA B L E 4 7 . 2 of fibrinolysis, which helps perpetuate the microthrombi and
fibrinous exudates that are pathognomonic for ALI.
CLINICAL DISORDERS ASSOCIATED WITH THE Injury to the alveolar epithelium plays a critical role in the
DEVELOPMENT OF ALI AND ARDS, pathogenesis of ALI. Through the loss of tight junctions and
SUBCATEGORIZED INTO THOSE COMMONLY barrier function, plasma proteins and edema fluid seep into
ASSOCIATED WITH DIRECT AND INDIRECT INJURY the alveolar space, leading to increased shunt fraction, higher
TO THE LUNG alveolar surface tension, and a greater propensity for alveo-
lar collapse. Clearance of both protein and fluid are crucial to
Direct injury Indirect injury the resolution of ALI. Indeed, a greater alveolar fluid clearance
(AFC) rate is associated with fewer days of mechanical ventila-
Common causes Common causes tion and lower mortality in patients with ALI [51]. The type I
Pneumonia Sepsis alveolar epithelial cell (pneumocyte) plays an important role in
Aspiration of gastric Severe trauma with shock barrier function, while the type II pneumocyte is the primary
contents and multiple transfusions source of surfactant production and is known to participate in
Uncommon causes Uncommon causes AFC. Although type I pneumocytes comprise 99% of the alve-
Pulmonary contusion Cardiopulmonary bypass olar surface area and are presumed to participate in AFC, their
Fat emboli Drug overdose exact role in this process remains undefined [52]. AFC occurs
Near drowning Acute pancreatitis by fluid following a sodium concentration gradient established
Inhalation injury Transfusion of blood by active sodium transport at the basolateral membrane via Na,
Reperfusion injury after products K-ATPase activity [53]. Despite the demonstrated impairment
lung transplantation of AFC in the setting of lung injury [54], areas of preserved
or embolectomy AFC can coexist with injury and epithelial barrier disruption
[55], making AFC a potential target for interventional therapy
Adapted from Ware LB, Matthay MA: The acute respiratory distress (see Management section).
syndrome. N Engl J Med 342:13341349, 2000, with permission. The resorption of protein from the alveolar space is believed
to occur more slowly than AFC, and is differentially regulated
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Chapter 47: Respiratory Failure Part II: Acute Respiratory Distress Syndrome 497

depending on the burden of protein present. Alveolar albumin Numerous additional pathways have been implicated in the
transport occurs primarily via receptor-mediated endocytosis pathogenesis of ALI, but an attempt to cover each in depth
at low concentrations, but occurs primarily via passive para- would extend beyond the intended breadth of this chapter. In
cellular diffusion when present in higher concentrations, as in brief, lipopolysaccharide (i.e., endotoxin) has long been rec-
the case of ALI [56]. Removal of larger insoluble proteins such ognized as a reliable initiator of ALI [82], particularly in the
as fibrin can take much longer and require degradation [56]. settings of sepsis and pneumonia, and the mechanisms of its ac-
On the other side of the alveolar capillary interface, injury tion have been extensively elaborated [83]. Oxidant-mediated
to the endothelium results in increased permeability, release of injury through the generation of reactive oxidant species is also
inflammatory molecules, expression of cell adhesion molecules, a well-recognized pathway for injury in ALI [84]. The cyto-
and activation of procoagulant pathways. Although endothe- protective role of the heat-shock response in ALI, particularly
lial injury is detectable under electron microscopy [19], gross through heat shock protein 70, is also widely acknowledged
endothelial damage may be seen only sparingly [48,57]. In- [85,86]. Dysregulated cell death and apoptosis through the re-
creased microvascular permeability has been widely demon- lease and accumulation of soluble Fas ligand is also thought to
strated in ALI [32,58,59], but this may be more due to a func- contribute to ALI and may also become a potential future tar-
tional alteration or activation of intact endothelium than due get for therapeutic intervention [49,87]. The role of mechanical
to actual cell lysis or necrosis. Endothelial cells can be activated ventilation in contributing to the development and worsening
by factors such as thrombin or endotoxin to increase surface of ALI is now also widely recognized and its mechanisms ex-
expression of the potent neutrophil-tethering molecules called tensively researched [88,89].
selectins [60] or to release preformed von Willebrand factor
(vWF) [61] and potent neutrophil activating factors [62]. En-
dothelial cell activation of binding molecules on neutrophils PATHOPHYSIOLOGY
can in turn promote their binding to the endothelium and trans-
migration into areas of injury. Furthermore, when endothelial Because of the accumulation of extravascular lung water
cells are tethered to activated neutrophils, such interaction can (i.e., pulmonary edema), the physiologic derangements of ALI
promote neutrophil degranulation [63], further contributing invariably manifest as refractory hypoxemia [90], decreased
to local injury and inflammation. The important role of en- respiratory compliance [91], and a propensity for alveolar clo-
dothelial activation in ALI is highlighted by the finding that sure [92]. As alveolar edema fluid and protein accumulate
elevated plasma levels of vWF have been shown to predict the within the alveoli, physiologic shunt develops as blood flows
development of ALI in patients at risk [64] and are associated through capillary units and perfuses alveoli that are either filled
with worse outcomes [65] and fewer organ failure-free days in with fluid, or have collapsed from the resulting increase in sur-
established ALI [65]. face tension (see Fig. 47.3A). Hypoxic vasoconstriction, the
Although widely accepted to play a key role in the patho- normal autoregulatory reflex that helps match ventilation and
genesis of ALI [50,66,67], the neutrophil is not essential for perfusion by shunting capillary blood flow away from poorly
the development of ALI, as evidenced by the development ventilated regions of the lung, is severely impaired within the
of ALI in the setting of neutropenia [68]. However, ALI can diseased regions of the lung [93]. Hence, physiologic shunt is
worsen during the recovery from neutropenia and after admin- accentuated by an imbalance of flow to the poorly ventilated
istration of the neutrophil growth and releasing factor, G-CSF lung regions [93]. Increased vasoconstriction and scattered mi-
[69]. Furthermore, neutrophil recruitment to the lung has been crothrombi within well-ventilated lung regions contribute to
shown to be a crucial factor in experimentally induced ALI physiologic dead space or wasted ventilation via diminished
as demonstrated by attenuated pathology under neutrophil- blood flow to aerated lung [93] (see Fig. 47.3B). The combined
depleted conditions [70,71]. effects of these derangements result in refractory hypoxemia
Activated leukocytes and endothelial cells can also con- and increased minute ventilation requirements, which explain
tribute to another recognized pathologic manifestation of the often challenging demands of managing these patients in
ALI: dysregulated intravascular and extravascular coagula- the intensive care unit.
tion [72,73]. Surface expression of tissue factor by alveolar Overall, the average pulmonary vascular resistance is
macrophages and endothelial cells can activate the extrinsic commonly elevated in patients with ALI [94,95], likely the
coagulation cascade through factor VII [73], activating throm- result of a reduction in total luminal diameter of the vascu-
bin and generating fibrin [72]. Extravascular alveolar fibrin lar bed, stemming from hypoxia and thrombotic obstruction
arising from increased procoagulant activity and impaired fib- [95,96]. This in turn leads to the common finding of pulmonary
rinolysis [74,75] has been well described in ALI [48]. Fibrin
formation and clearance in the lung is in part governed by
the differential activity of fibrinolysis promoters and inhibitors
[7476]. Plasminogen activators enzymatically convert plas-
minogen to active plasmin, the key protease involved in fibri-
nolysis. Plasminogen activator inhibitor-1 (PAI-1) can prevent
fibrinolysis via direct binding and inhibition of plasminogen
activators [77]. PAI-1 inhibition of fibrinolysis in the BAL fluid
of ALI patients was first recognized in 1990 [75]. Since then
the importance of PAI-1 in ALI has been further recognized in
that elevated plasma and edema fluid levels of PAI-1 are as-
sociated with higher mortality in ALI patients [78]. However,
studies examining the direct role of PAI-1 in animal models
of ALI have yielded mixed results [79,80]. With respect to the A B
initial process of coagulation and fibrin generation, the activa-
FIGURE 47.3. A: The edema fluid-filled alveolus and a neighboring
tion and expression of tissue factor (TF) has received notable
collapsed alveolus, both with unrestricted blood flow, contributing
attention due to its known interaction with factor VIIa and to physiologic shunt. Double-headed (arrow) represents potential for
downstream generation of thrombin. TF expression has been fluid-filled alveolus to collapse and re-expand during normal tidal ven-
shown to be increased on the surface of alveolar epithelial cells tilation. B: The effect of a microthrombus (black oval) obstructing
and macrophages in patients with ALI, and is accompanied by blood flow to a functioning alveolus, contributing to physiologic dead
increased procoagulant activity in the edema fluid [81]. space.
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498 Section IV: Pulmonary Problems in the Intensive Care Unit

hypertension in these patients, which can alter right ventricular can also be seen as an expansion in the hysteresis of pressure
loading and function [94,97], and predicts higher mortality in volume (PV) curves obtained during graded inflation of the
afflicted patients [97]. Because elevated pulmonary artery pres- lung (see Fig. 47.4). The decrease in slope of the inspiratory
sures could in theory contribute to increased pulmonary edema limb of the PV curve represents a decrease in volume obtained
[94,98] and right heart strain, it is unclear whether pulmonary for any given change in pressure, and hence a decrease in com-
hypertension is directly contributing to mortality or simply a pliance.
marker of disease severity [95].
The mechanical manifestations of ALI present mainly as a
decrease in respiratory compliance. This is primarily due to MANAGEMENT
a decrease in lung compliance, particularly in the more direct
forms of ALI such as pneumonia. However, contribution from Mechanical Ventilation
the chest wall and abdominal compartment can be significant
under conditions such as trauma and peritonitis [38]. The re-
duction in lung compliance reflects the collective contribution
Mechanical Ventilation and Low Tidal Volumes
of changes in the intrinsic elastic properties of the remaining The early presentation of ALI is chiefly characterized by hypox-
aerated lung and a reduction in resting lung volume via alve- emic respiratory failure and the almost invariable need for sup-
olar flooding and collapse. The increased elastic properties of port with mechanical ventilation. Because the greatest danger
the aerated lung result from increased tissue stiffness due to in- posed to patients with ALI is the development of multiorgan
terstitial edema and increased alveolar surface tension, but the failure [110], establishing supportive ventilation modes that
contribution from interstitial edema is thought to be negligible optimize hemodynamic function and oxygen delivery remain
relative to that from alveolar edema [99]. The increase in alve- important objectives in the management of these patients. Prior
olar surface tension is thought to develop from the increased to the late 1960s, endotracheal intubation and positive pres-
surface forces generated by a greater abundance of alveolar sure mechanical ventilation were primarily used for supporting
lining fluid and a decrease in surfactant activity [100]. This patients during general anesthesia. It was during this time that
loss in surfactant activity is believed to result from inhibitory investigators first noted that larger tidal volumes could reduce
binding of surfactant by plasma proteins [101] and cholesterol the shunt associated with atelectasis during general anesthe-
[102], and decreased production of functionally active surfac- sia [111]. Soon afterward, the benefits of a larger tidal volume
tant by type II pneumocytes [3,103]. To further complicate on shunt were demonstrated in animal models of ALI [112].
matters, the biomechanical effects of mechanical ventilation Because many of the techniques used for the support of pa-
alone can alter the structure and biophysical properties of sur- tients with acute respiratory failure were originally adopted
factant [104,105], an unfortunate consequence of a typically from general anesthesia practice, employing tidal volumes of
mandatory intervention for this condition. 10 to 15 mg per kg became the standard for improving oxy-
Lower resting lung volumes in ALI result from persistently genation and ventilation in patients with ALI [113,114].
fluid filled or collapsed alveoli, leading to what has been collo- We now know that idealized oxygenation and normal phys-
quially referred to as baby lung [106]. The affected regions iologic pH and PaCO2 can come at a cost when employing
of the lungs are often so diseased that they may remain fluid- higher tidal volumes in patients with ALI. After VILI was in-
filled or collapsed throughout each tidal inflation [107] and duced with higher tidal volumes in animal models [88,115],
hence contribute negligibly to compliance. In fact, CT imaging small retrospective and prospective uncontrolled trials sug-
has demonstrated respiratory compliance to be more closely gested a benefit from limiting tidal volume and peak airway
linked to the amount of aerated lung [108], lending some to as- pressures in patients with ALI [116,117]. Numerous larger,
sert that compliance is more of a direct measure of aerated lung randomized trials comparing traditional and lower tidal vol-
volume than tissue stiffness [106]. As a result, tidal volumes de- umes have since been conducted, each trial differing in its
livered to the heterogeneously fluid-filled and atelectatic lung methodology and results [1,2,118120]. The largest random-
are shunted preferentially to more compliant, aerated regions ized, multicenter trial to date, conducted by the ARDS Net-
of the lung [109]. This is one of the main postulated mecha- work, ultimately demonstrated a significant reduction in mor-
nisms through which mechanical ventilation can overdistend tality when using a tidal volume of 6 mL per kg of predicted
and injure the remaining regions of normal lung and lead to ideal body weight and a target plateau pressure of 30 cm H2 O
ventilator-induced lung injury (VILI) [88]. or less (mortality 31.0%) as opposed to a tidal volume of 12
At the bedside, the reduction in compliance is typically ob- mL per kg and a target plateau pressure less than 50 cm H2 O
served as an increase in peak and plateau airway pressures but (mortality 39.8%) [1].
In an effort to better understand the protection conferred
by low tidal volumes, investigators have studied how this strat-
egy modulates the inflammatory cascades associated with ALI
and VILI. Evidence now exists to support the theory that low
tidal volume ventilation improves outcomes at least in part
through reduced activation of the inflammatory cascades asso-
ciated with VILI and multiorgan failure. For instance, among
patients enrolled in the ARDS Network trial of low tidal vol-
ume, it was found that higher plasma levels of soluble recep-
tors for tumor necrosis factor- (TNF-) were associated with
higher mortality and fewer organ-failure free days [121]. Fur-
thermore, the lower tidal volume strategy was associated with
lower levels of soluble TNF- receptor I [121]. In another study
from the same patient population, elevated plasma levels of in-
FIGURE 47.4. Simulated pressure volume curve obtained from typical
acute lung injury patient, with pressure recorded during slow inflation
terleukin (IL)-6, 8, and 10 were also linked to increased mor-
to total lung volume. Lower inflection point (LIP) marked at point of tality while lower tidal volume was associated with a greater
sudden change in slope of inflation curve. Point of maximal curvature drop in IL-6 and IL-8 by day 3 of enrollment [122].
(PMC) also marked at point of maximal change in slope of deflation Many studies of low tidal volume ventilation adopted a
curve. strategy of permissive hypercapnia, in which investigators
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tolerated a reduction in minute volume and an ensuing in- [134,140], recent larger trials have demonstrated more promis-
crease in PaCO2 to achieve lower target tidal volumes and air- ing improvements in lung function and oxygenation but still
way pressures [117,118,120]. Most studies suggest that this failed to demonstrate any reduction in mortality [146,147]. Al-
strategy is safe [117,118], but the actual safety of this prac- though no guidelines currently exist, it is important to note that
tice is not yet entirely known. Although some animal studies patients with ALI of differing origin [38,136,148] and stages
have demonstrated a potential protection by hypercapnic aci- of injury [141] vary in their response to RM, and it may help
dosis [123,124], others suggest that hypercapnic acidosis may to first differentiate responders from nonresponders [141,148].
worsen ALI and VILI [125,126]. Some guidelines acknowledge When performed, RMs are traditionally delivered as sustained
permissive hypercapnia as an acceptable practice when neces- inflations with peak inflation pressures limited to between 30
sary to limit tidal volumes, but also stress that its use is limited and 40 cm H2 O, and held for a period ranging from 15 to 40
in patients with preexistent metabolic acidosis, and contraindi- seconds [2,141,144].
cated in patients with increased intracranial pressure [127]. Be-
cause no firm guidelines have been established, current options
Positive End-Expiratory Pressure
range from a allowing for an arterial pH as low as 6.8 [117],
to increasing respiratory rate up to 35 and buffering with in- PEEP is another widely employed strategy shown to retard alve-
travenous bicarbonate when pH drops below 7.3 [1]. Despite olar derecruitment in the injured lung. Several studies have
ongoing controversy [128] and the delayed adoption low tidal demonstrated the ability of PEEP to prevent or delay alveolar
volume strategy in clinical practice [129,130], the current ev- derecruitment [149,150] and attenuate VILI [115,151]. How-
idence has led professional societies to recommend the use of ever the protective effect of higher PEEP was called into doubt
lower tidal volumes at goal plateau pressures less than 30 cm after a multicenter randomized trial failed to demonstrate an
H2 O in patients with established ALI [127]. Because calcula- improvement in outcomes using a higher PEEP strategy dur-
tions based on total body weight may be partly responsible for ing low tidal volume ventilation in ALI patients [152]. In this
the documented underuse of lower tidal volumes for patients NHLBI-sponsored trial, higher levels of PEEP were arbitrar-
with ALI [129], the importance of using predicted ideal body ily coupled to each step-wise increment in FiO2 requirement
weight (IBW), based upon measured height and sex, cannot be during low tidal volume ventilation [152]. The study failed
overstressed. IBW (in kg) for males is calculated as 50 + 0.91 to demonstrate any benefit in mortality or ventilator-free days
((height in cm)152.4), and for females as 45.5 + 0.91 ((height with higher PEEP [152], but potential underpowering of this
in cm)152.4) [1]. Although no firm guidelines exist regard- study has left room for continued debate [153]. In addition,
ing patients without established ALI, there is clinical evidence since the amount of recruitable lung varies significantly among
that a low tidal volume strategy may help prevent progression ALI patients [154], some have suggested that setting PEEP lev-
to ALI in patients at risk [131,132]. Yet to be determined is els without first determining the level of recruitable lung may
whether a more optimal or best strategy exists beyond that offset the potential benefits of PEEP. In a recent randomized
employed in the ARDS Network sponsored study. Although trial, the selection of PEEP was more patient-directed and set
data suggest that tidal volumes lower than 6 mL per kg may at a level required to maintain plateau pressures of 28 to 30 cm
confer even greater protection from VILI [133], there is no gen- H2 O [147]. This higher PEEP strategy again failed to demon-
eral consensus on this practice. However, the authors note that strate a reduction in mortality, but did demonstrate lasting im-
in the original ARDS Network trial, the lower tidal volume provements in oxygenation and compliance and an increase in
assignment started with a goal of 6 mL per kg, but patients in ventilator-free and organ failure-free days [147]. Others have
this arm were oftentimes adjusted to as low as 4 mL per kg as shown that more directly targeting PEEP to transpulmonary
needed to maintain plateau pressures less than 30 cm H2 O [1]. pressure by measuring esophageal pressures may be a safer and
more effective means of determining optimal PEEP [155].
This raises the question of how one determines the opti-
Recruitment mal setting of PEEP. The often observed lower inflection point
The physiologic abnormalities in ALI can, in some patients, be (LIP) on the inspiratory limb of the PV curve obtained from
reversed by a recruitment maneuver (RM), typically delivered ALI patients is the point beyond which the slope of the curve
as a sustained deep inflation with the intention of reopening dramatically increases (see Fig. 47.4). This dramatic increase
collapsed regions of the lung. However, because of the unusu- in compliance at the LIP was initially believed to represent
ally high surface tension within affected alveoli, the benefit is a sudden increase in lung volume and hence maximal alveo-
often transient [134,135], especially if not followed by suffi- lar recruitment. Thus, many have advocated using the LIP to
ciently high levels of PEEP [136]. The potential impact of RMs guide the setting of optimal PEEP [2,156]. However, several
on morbidity and mortality is not trivial. In fact, because dere- studies have demonstrated significant recruitment beyond the
cruitment leads to an effectively smaller ventilated lung, inves- LIP [157,158], a concept supported by mathematical models
tigators have proposed the use of open lung strategies [137] [159] and CT imaging [108,160]. Data from CT imaging in
with periodic delivery of RMs to limit regional overdistention ALI patients has recently lent strong support to setting opti-
and minimize injury from atelectasis and cyclic alveolar reex- mal PEEP at the point of maximal curvature (PMC) along the
pansion [88]. The long-term effect of atelectasis in humans is deflation limb of the PV curve [160] (see Fig. 47.4). Neverthe-
unclear, but prolonged periods of atelectasis have been shown less, the concept of optimal PEEP has likely been oversim-
to promote vascular leak and right ventricular failure in rodents plified and controversy remains over how alveolar recruitment
[138]. On the other hand, periodic RMs also have the poten- is best served by PEEP.
tial to worsen oxygenation by shunting blood flow to poorly
aerated regions [139] and impair cardiac output by limiting ve- High-Frequency Ventilation and Extracorporal
nous return and cardiac preload [140,141]. Furthermore, RMs
could conceivably contribute to lung injury through excessive
Membrane Oxygenation
overdistention [142] or repeated opening of collapsed lung. With the data demonstrating a reduction of mortality with
Despite encouraging findings from animal studies [143, a low tidal volume strategy in humans and animal studies
144], clinical studies have yielded mixed results regarding showing that even lower tidal volumes offer additional pro-
beneficial effects of RMs on oxygenation and lung function tection [133], high-frequency oscillation ventilation (HFOV),
[134,141,145]. Although earlier clinical studies demonstrated with very small tidal volumes equal to or less than dead space
the benefits of recruitment to be negligible or short-lived and delivered at a very high rate, would seem to be an ideal
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500 Section IV: Pulmonary Problems in the Intensive Care Unit

ventilatory strategy in ALI. How adequate ventilation is not entirely clear. Proposed mechanisms have centered around
achieved with tidal volumes less than or equal to dead space the potential reversal of gravitationally distributed perfusion to
is unknown. Proposed mechanisms include a pendelluft effect the better ventilated ventral lung regions [184] and improved
of mixing gases between lung regions of differing impedances, ventilation of previously dependent dorsal lung [185], both
coaxial flow with net center inflow and net peripheral outflow, of which would improve ventilation/perfusion matching. Curi-
mixing of fresh and residual air along the leading edge of gas ously, however, prone positioning exerts limited gravitational
flow, and simple molecular diffusion through relatively still air effects on regional perfusion in either normal or injured lung
[161]. HFOV first demonstrated clinical benefits among in- [186] but can sufficiently increase dorsal transpulmonary pres-
fants with respiratory distress syndrome [162,163]. Although sures to improve ventilation within previously dependent dor-
early smaller studies of HFOV in adult ALI were promising sal regions of the lung [185]. Proposed mechanisms for this
[164,165], a larger multicenter-controlled trail failed to demon- improvement in dorsal ventilation include a reduction in de-
strate any reduction in mortality from HFOV over conven- pendent lung compression by the heart and mediastinum [187]
tional ventilation [166]. Nevertheless, newly developing strate- and regional changes in chest wall mechanics [188].
gies and equipment allow room for ongoing investigation of In animal models, prone positioning reduces physiologic
HFOV for adult ALI. shunt [187], protects against VILI [189], reduces PEEP require-
Extracorporeal membrane oxygenation (ECMO), used ments [190], and attenuates perfusion imbalances imposed by
alone or in combination with HFOV, uses cardiopulmonary added PEEP [191]. Despite these known physiologic benefits,
bypass to facilitate gas exchange while minimizing ventilation the first large randomized clinical trial of prone positioning
of the lung to limit barriers to healing. Despite demonstrated demonstrated a significant improvement in oxygenation but
efficacy in neonates with severe respiratory distress syndrome no improvement in survival [192]. Post hoc analysis suggested
[167], ECMO had until recently failed to demonstrate any re- an early survival advantage in the most severe subgroup of
duction in adult mortality [168,169]. The largest controlled patients, which has also been suggested by subsequent stud-
trial to date in ECHO for severe adult ARDS recently demon- ies [193]. The largest randomized clinical trial to date also
strated an improvement in 6-month survival without disability demonstrated an improvement in oxygenation and a reduced
when compared to conventional ventilatory support [170]. De- incidence of ventilator-associated pneumonia with prone posi-
spite noted strengths in study design, the lack of protocolized tioning, but again no benefit in survival [194]. This study, how-
ventilator and critical care management in the control group, ever, brought greater attention to safety concerns by demon-
along with prohibitive issues of cost and availability has led strating a higher incidence in pressure sores and inadvertent
experts to predict negligible resulting change in clinical use of endotracheal tube displacement. Some experts still advocate
this still controversial intervention [171]. an investigation of prone positioning in patients with severe
ARDS [195], but the indiscriminant use of prone positioning
Noninvasive and Partial Support Ventilation for the general ALI population is not well supported by the
current literature [192,194].
As described earlier, the physiologic shunt responsible for re-
fractory hypoxemia in ALI is attributed in part to alveolar
collapse without adequate compensatory decrement in perfu- Fluid Management
sion within the gravitationally dependent lung [172]. Nonin-
vasive ventilation (NIV) and partial support ventilation modes Fluid management in ALI is an ongoing topic of controversy.
such as pressure support ventilation, allow for patient trig- Because pulmonary edema is the hallmark of ALI, it seems rea-
gering and cycling of breaths, resulting in more spontaneous sonable to aspire to keep patients relatively dry. However,
breathing. The potential advantages of spontaneous breath- because the development of multiple organ dysfunction syn-
ing over controlled mechanical ventilation include improved drome (MODS) increases mortality from ALI, the critical main-
patientventilator synchrony, lower sedation requirements, tenance of adequate peripheral perfusion may require liberal
and improved hemodynamics and ventilation/perfusion (Va/ Q) administration of intravenous fluid. The type of fluid to admin-
matching [173,174]. Partial assist modes of ventilation can ister is also controversial. As pulmonary edema is dependent
still effectively help unload respiratory workload while allow- on both hydrostatic and oncotic forces, the issues of optimal
ing for variable degrees of spontaneous breathing [175,176]. fluid balance and replacement of plasma colloid are not triv-
These modes have also been shown to improve aeration and ial. Diuretic therapy with combined albumin and furosemide
ventilation/perfusion matching within dependent lung regions has been shown to improve oxygenation and hemodynamics
[177], presumably due to more pronounced transpulmonary in hypoproteinemic ALI patients but does not reduce mortality
pressures generated within these regions by an actively moving [196]. In another study comparing the administration of albu-
diaphragm [178]. min and furosemide with furosemide alone, a greater improve-
When these modes are applied noninvasively by face mask, ment in oxygenation was seen with albumin plus furosemide
an added benefit is the potential reduction in infectious com- [197]. This suggests that albumin may either potentiate the ef-
plications, namely nosocomial pneumonia [179]. Studies have fects of furosemide, allow for better tolerance of diuresis, or
shown that NIV can be used safely for the treatment of ALI confer other favorable effects on oxidant balance [198] or en-
[180,181]. In a recent multicenter nonrandomized trial, the dothelial permeability [199]. The NHLBI ARDS Network trial
use of NIV as first line treatment for ALI helped to avoid intu- of conservative versus liberal fluid management demonstrated
bation in 54% of cases and led to a reduction in the incidence no difference in 60-day mortality between the two different
of VAP [182]. However, authors could not recommend NIV in strategies [200]. However, the patients in the conservative strat-
patients with a SAPS (Simplified Acute Physiology Score) II of egy group had a lower 7-day cumulative fluid balance with
greater than 34 due to a high rate of failure in this group. improved lung function and a reduced duration of mechanical
ventilation without an increase in nonpulmonary organ failure
[200].
Prone Positioning An additional controversy is what parameter should be used
to guide fluid management. Whether the indwelling pulmonary
Prone positioning was shown to improve oxygenation in pa- artery (PA) catheter is vital to the management of ALI depends
tients with hypoxic respiratory failure as early as the mid-1970s upon two important considerations. First, optimal fluid bal-
[183], but how prone positioning improves oxygenation is still ance must be crucial to preventing the progression of lung
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Chapter 47: Respiratory Failure Part II: Acute Respiratory Distress Syndrome 501

injury. Although this seems defensible in theory, it has yet to be benefits at lower doses, experts recommend using iNO at doses
proven. Second, these indwelling catheters must provide a crit- less than 10 ppm when used as rescue therapy.
ical and unique understanding of this balance that sufficiently
and appropriately modifies clinical practice. This has also yet
to be proven. The use of PA catheters came into question af-
Surfactant Replacement
ter a large observational study of 5,700 critically ill patients Not long after ALI was first described [213] investigators
actually suggested a higher mortality rate associated with PA demonstrated a reduction in the amount of surfactant retrieved
catheter use [201]. However, subsequent prospective trials have from the lung and a derangement in the retrieved surfactants
contradicted these findings [202,203]. Unfortunately, the lack biophysical properties [100]. Since then, numerous studies have
of any clear protocol regarding when to place these lines, and supported these findings. The chief surface-tension lowering
how to interpret and adjust management according to the in- components of surfactant are phospholipids that align their
formation provided, leaves ongoing uncertainty regarding their hydrophilic polar heads along the surface of the alveolar lining
use in patients with ALI [204]. Results from the ARDS Net- fluid and reduce surface tension by interfering with the lat-
work trial suggest that PA catheter-guided therapy does not eral forces imposed upon the alveolus by water tension. Phos-
improve survival in ALI patients and is associated with more phatidylcholine (PC) makes up the majority of the phospho-
complications than the use of central venous catheters alone lipid fraction, followed in abundance by phosphatidylglycerol
[205]. (PG) [214]. The large aggregate fractions consist of large lamel-
lar structures, tubular myelin, and surfactant-associated pro-
teins, and possess the primary surface-tension lowering prop-
Pharmacologic Intervention erties, while the smaller aggregates contain smaller lipids, less
surfactant protein, and have limited surface activity [215,216].
As in any other medical disease or syndrome, it would seem In ALI, the relative amount of large-to-small aggregates is
that the Holy Grail among clinicians is the discovery of some reduced [215], as are amounts of bioactive PC and PG
novel agent that can either break the cycle of disease pathogen- [215].
esis or help restore physiologic homeostasis and reduce disease Surfactant-associated proteins also play varied and impor-
severity and morbidity. The field of pharmacologic interven- tant roles in surfactant function. Surfactant protein A (SP-A)
tion has been exhaustively explored in the field of ALI, often has been implicated in formation of tubular myelin and antimi-
yielding promising results in animal models and periodically crobial defense [217]. SP-B helps to enhance the distribution
demonstrating modest improvements in lung function and oxy- and stability of phospholipids within the airliquid interface
genation in patients, but rarely translating into improved out- [218]. SP-C is hydrophobic and believed to closely interact with
comes. the surfactant film [219]. Bronchoalveolar lavage fluid (BAL)
levels of SP-A and SP-B are reduced in patients with established
ALI and those at risk [220]. At the same time, serum levels of
Pulmonary Vasodilators SP-A and SP-D are typically elevated in these patients [220]
Given the advanced endothelial injury, physiologic shunt, and and such elevations are associated with more severe disease
commonly observed pulmonary hypertension in ALI, there has and increased risk of mortality [221].
been extensive investigation into the therapeutic benefit of The fundamental rationale for surfactant replacement is to
pharmacologic pulmonary vasodilatation. Initial studies exam- help restore the natural surfactant film and reduce surface ten-
ined the use of intravenously administered vasodilators such sion at the airliquid interface, thus reducing the tendency for
as nitroglycerin and prostacyclin [98,206], but simultaneous alveolar collapse and improving oxygenation through a reduc-
and nonselective reductions in systemic and pulmonary vas- tion in shunt. The evidence in support of surfactant replace-
cular resistance led to systemic arterial hypotension with in- ment therapy for neonatal RDS is abundant [222,223]. Results
creases in cardiac output and shunt. After the once described from its investigated use in adult ALI patients have been less
endothelial-derived relaxing factor was discovered to be ni- promising [3,224,225]. Some have speculated that the failure
tric oxide (NO) [207], it was found that inhaled NO (iNO) to demonstrate an improvement in mortality is due to the lack
could selectively dilate the pulmonary vasculature within well- of a direct relationship between mortality and severity of res-
ventilated regions of the lung [208], helping reverse both hy- piratory failure alone [110,226]. However, under the assump-
poxic vasoconstriction and physiologic shunt. Subsequently, tion that alveolar collapse promotes progression of ALI during
two small-randomized controlled trials demonstrated a signif- mechanical ventilation, many believe that restoring surfactant
icant but transient improvement in oxygenation and shunt in function holds promise in reducing morbidity and mortality by
ALI patients in response to iNO, but these benefits did not attenuating VILI. In fact, there is evidence from animal mod-
last past 24 hours, and there was no improvement in out- els that surfactant replacement therapy may help prevent VILI
comes [209,210]. A larger multicenter trial failed to demon- [227,228]. Current obstacles to demonstrating this benefit in
strate a reduction in mortality or ventilator-free days when patients are imposed by intricacies of surfactant administra-
pooled data from all iNO dosing groups were compared with tion and its potential inactivation by plasma proteins follow-
placebo [211], but the subgroup receiving 5 ppm iNO showed ing delivery. For example, although there is improvement in
improvement in these parameters. A larger European trial of lung function following surfactant replacement [229], the re-
iNO has since demonstrated a reduction in the development sponse is transient. This has been, at least in part, attributed
of severe respiratory failure but no reduction in mortality to the tendency for the administered surfactant to be inacti-
[212]. vated by plasma proteins in the airspace following [230,231].
Most studies have demonstrated minimal adverse effects of This obstacle has been addressed, with mixed results, by adding
iNO other than dose-dependent methemoglobinemia [211]. At surfactant proteins [231,232] or polyethylene glycol [233] to
the present time, iNO has been approved by the Food and Drug block serum protein binding of surfactant.
Administration for use in neonates with hypoxic respiratory Despite ostensibly warranted enthusiasm, the largest mul-
failure accompanied by pulmonary hypertension but is not ap- ticenter randomized clinical trial in adult ALI failed to
proved for use in adult ALI. Experts have concluded that iNO demonstrate any improvement in mortality with continuous
can improve oxygenation in the early phase of its application aerosol delivery of the synthetic surfactant, Exosurf [224]. An-
with minimal adverse effects and is a feasible rescue therapy other large-scale, randomized investigation of intratracheally
in severe and refractory ARDS [93]. Given the demonstrated delivered, recombinant SP-C in ALI patients demonstrated
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502 Section IV: Pulmonary Problems in the Intensive Care Unit

improvement in oxygenation but again no reduction in mor- most recent phase II clinical trial failed to demonstrate a reduc-
tality or duration of mechanical ventilation [3]. Nevertheless, tion in ventilator-free days with the use of APC [254]. Critics
many investigators believe that a strong case can still be made expressed concern about the studys statistical power and a pri-
for further research in surfactant replacement strategies [226]. ori likelihood of success [255], but in a similar vein, despite a
promising animal studies [244,250], a recent multicenter Phase
Corticosteroids II trial of Tissue Factor inhibitor (site-inactivated VIIa) in ALI
was terminated prematurely due to higher projected mortality
Given the well-characterized acute inflammatory response of
rates in the high-dose treatment arm [256]. There was also an
ALI and evidence that a fibroproliferative response can predict
increased risk of adverse bleeding events with escalating doses
worse outcomes [23,24], considerable effort has been spent
of this drug [256]. Thus, it seems that the benefits of potent
determining the therapeutic role of corticosteroid therapy for
anticoagulation in ALI may ultimately be outweighed by risks
this condition. The use of steroids for ALI dates back to the
of adverse bleeding, but further investigation is warranted.
original report of this condition in 1967, when Ashbaugh
and Petty suggested a potential role for corticosteroids in fat-
embolism and viral-related ALI [213]. Ashbaugh later drew
parallels between the features of persistent ALI and idiopathic
-Agonists
pulmonary fibrosis, and noted the potential for treating these As discussed in the pathogenesis section, AFC often remains
patients with corticosteroids [234]. Numerous uncontrolled intact in the setting of injury. AFC can be directly increased
trials had initially suggested a potential benefit of corticos- by -agonists in animal models [6,257], presumably through
teroids for late or persistent ARDS [235237]. However, treat- upregulated activity of Na, K-ATPase at the basolateral mem-
ment with corticosteroids during the acute phase of ALI has brane [258]. In human subjects, the use of exogenous cate-
since been proven ineffective [238,239]. The first randomized cholamines has been retrospectively linked to increased AFC
controlled trial of corticosteroids for late ARDS demonstrated [51], but, until recently, the greatest support for pharmacologic
improved lung injury scores and oxygenation, decreased mul- AFC modulation in ALI came indirectly from findings of lower
tiorgan dysfunction scores, and reduced ICU and in-hospital mortality in ALI patients having preserved/maximal AFC [51].
mortality in the group receiving steroids [240], but this study An early study demonstrated reduced extravascular lung wa-
drew criticism for its small size and baseline differences be- ter in patients receiving intravenous salbutamol, but treatment
tween the treatment groups [241]. Since then, a significantly was complicated by supraventricular tachyarrhythmias [259].
larger NHLBI sponsored multicenter trial completed by the A large multicenter randomized trial investigating the use of
ARDS Network exploring the use of corticosteroids for late the aerosolized -agonist, albuterol, for the treatment of ALI,
persistent ARDS demonstrated more ventilator-free days and was recently halted on the basis of projected futility [260]. In
improved oxygenation in the group treated with methylpred- the wake of findings, there is currently no support for the use
nisolone compared with placebo, but no reduction in 60-day of -agonists in the treatment of ALI.
mortality [242]. Furthermore, a higher 60- and 180-day mor-
tality was observed when steroid therapy was initiated after
14 days of onset, suggesting a serious risk from this therapy Nutritional Supplementation
for late ARDS.
Over the past decade, enthusiasm has arisen over the use of nu-
tritional supplements in sepsis and ALI, particularly with the
Anticoagulation/Fibrinolysis use of omega-3 fatty acids and other natural antioxidants such
The importance of microvascular coagulation and thrombosis as vitamin E. The rationale for supplementing patients with
in ALI is underscored by the physiologic dead space, or wasted omega-3 fatty acids, such as eicosapentaenoic acid (EPA), in the
ventilation, observed in ALI patients [243]. Minimizing mi- setting of inflammatory disorders comes from the notion they
crovascular thrombosis could conceivably improve oxygena- can directly suppress monocyte production of inflammatory cy-
tion through improved ventilationperfusion matching [244] tokines and incorporate into cell membrane phospholipids to
and increase survival through prevention of multiorgan failure compete with omega-6 fatty acids to promote the production of
[245]. Thus, the importance of coagulation in the pathogenesis more favorable prostaglandins and leukotrienes [261]. Perhaps
of ALI has become widely appreciated [72], and the use of an- the most encouraging earlier data supporting omega-3 fatty
ticoagulant therapy in ALI has in turn gained attention [246]. acids in ALI came initially from small randomized trials com-
Although it has been shown that fibrin and its degradation paring a standard isonitrogenous, isocaloric enteral diet with
products can promote inflammation [247], vascular leak, and one supplemented with a proprietary mixture of EPA, gamma-
wound remodeling [72], the detriment imposed by alveolar fib- linolenic acid (borage oil), and other antioxidants [262264].
rin has also been accredited to its recognized in vitro capacity These studies demonstrated an improvement in gas exchange
to bind with and inhibit the surface-tension lowering capacity and lung function [262,264], a reduction in BALF levels of IL-8,
of surfactant [248,249]. This has led to considerable interest leukotriene B4 , and neutrophils [263], and a reduction in ICU
in limiting in situ fibrin deposition as a means of preserving stay and mechanical ventilation days [262] with the EPA-rich
lung function [246]. As a result, several different anticoagulat- supplement.
ing agents have been investigated in animal models, some of An effort was made to better clarify the effects of omega-3
which have been shown to attenuate lung injury and improve fatty acids alone in a randomized controlled trial comparing the
survival [244,250,251]. use of EPA and docosahexanoic acid with a nonnutrient saline
The most encouraging clinical evidence to support this ther- supplement. This study failed to demonstrate any associated
apeutic target initially came from a multicenter trial demon- benefit in their a priori primary outcome (BALF IL-8 and LTB4
strating a mortality benefit from activated protein C (APC) levels), but it did show a yet unexplained trend toward a reduc-
in severe sepsis [245]. However, because randomized trials of tion in ICU length of stay and days on mechanical ventilation
other potent anticoagulants, such as antithrombin III and tissue [265]. The largest trial of supplemental omega-3 fatty acids to
factor pathway inhibitor (TFPI), yielded no mortality benefit in date, conducted by the ARDS Network, was recently halted
sepsis [252,253], the postulated benefits from APC may be un- early due to projected futility [266], but the other component
related to its anticoagulant activity. Consequently, investigators of this study investigating early versus delayed enteral feeding
have focused on the use of APC for ALI that is not accompanied in ALI remains ongoing. Reasons for these negative findings
by sepsis. Despite promising results in a rat model [251], the are not yet well understood.
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Chapter 47: Respiratory Failure Part II: Acute Respiratory Distress Syndrome 503

retrospective study of patients on statin therapy at the time


PROSPECTIVE FUTURE THERAPIES of ALI diagnosis that demonstrated a 73% reduction in odds
of death, but this did not reach statistical significance [292].
Airway Pressure Release Ventilation A large, randomized placebo-controlled trial is currently be-
ing conducted by the NHLBI ARDS Clinical Trials Network
Airway pressure release ventilation (APRV) is a mode of ven- (ClinicalTrials.gov Identifier: NCT00979121).
tilation that uses sustained high airway pressures and spon-
taneous breathing to maximize lung recruitment, with brief Preemptive Intervention Protocols
periods of pressure release to facilitate ventilation while min-
imizing derecruitment during exhalation [267]. Proponents as- The search for an effective pharmacologic intervention or man-
sume that the periods of pressure release are brief enough to agement algorithm in ALI has thus been extensive and has
avoid alveolar closure and reexpansion [268], and efficacy re- now spanned decades. Despite this effort, with the exception of
lies heavily on the presence of spontaneous ventilation [269], low tidal volume ventilation, the reward from most interven-
which is believed to generate regionally variable transpul- tions has been limited to improvements in oxygenation [3,192]
monary pressures that favor recruitment of dependent lung or fewer days of mechanical ventilation [147,200] (see Table
regions [174]. Although APRV can be equally efficacious and 47.3). One important lesson from the work to date is that much
safe when compared with SIMV and pressure support modes of what we once thought was critical to the management of
[174,270], most published experience in ALI with this mode these patients, although grounded in sound rationale, is not
has been in the surgical and trauma population [174,271,272], only often ineffective, but can also be potentially harmful. We
and the same findings may not hold true for more unstable have become more aware of how sound basic and simple prin-
forms of ALI resulting from direct pulmonary injury, such as ciples of ICU care, such as hand hygiene and protocols for
pneumonia and aspiration.Fortunately, two studies comparing ventilator-associated pneumonia prevention can substantially
APRV with conventional low tidal volume ventilation in ALI reduce overall morbidity in the ICU [293,294]. In keeping with
are currently enrolling patients (ClinicalTrials.gov Identifiers this philosophy of preemptive intervention, two studies have re-
NCT00750204 and NCT00793013). cently demonstrated that something as simple as early interven-
tion with physical therapy in mechanically ventilated patients
is not only safe and cost-effective, but can also reduce the du-
Stem Cell Therapy ration of delirium, mechanical ventilation, ICU and hospital
Recent attention has been given to use of bone marrow derived length of stay, and promote greater functional independence
and circulating stem cells in an effort to expedite tissue regener- by the time of discharge [295,296]. Investigators have also dis-
ation through engraftment and suppress inflammation through covered reductions in ALI incidence following the enforcement
immunomodulation [273]. Enthusiasm first came from findings of conservative transfusion policies (prevention of TRALI) and
suggesting a favorable rate of engraftment and epithelial differ- preemptive low tidal volume ventilation (prevention of VILI)
entiation of infused bone marrow derived stem cells in the in- in the care of patients at risk for the development of ALI
jured lungs of mice [274]. Important clinical findings followed [131,132]. Such practice seems compatible with an emerging
with the discovery that circulating epithelial progenitor cells theme that if clinicians are still limited to supportive care for
(EPCs) are elevated in the plasma of patients with ALI, and ALI patients, then they should at least be doing less harm by
that increased circulating EPCs are associated with reduced delivering lower tidal volumes [1], limiting transfusion of blood
ALI mortality [275]. Newer studies suggest that the rates of products, [132,297], conservatively limiting fluids in stable re-
stem cell engraftment and differentiation are not as robust as suscitated patients [298], and fastidiously preventing iatrogenic
initially hoped, but many are examining ways of promoting infections [299].
engraftment [273]. This field has found added momentum in
the discovery that infused bone marrow derived stem cells may
also down regulate inflammation and dampen ALI progression,
independent of engraftment [276].
PROGNOSIS AND OUTCOMES

HMG-CoA Reductase Inhibitors (The Statins) Prognosis


Recent animal experiments and observational human studies Numerous clinical factors have been shown to predict a higher
have provoked interest in the treatment of ALI with HMG-CoA mortality rate in ALI patients. These include male sex, African
Reductase Inhibitors (also called statins), a class of drugs American race, advanced age, alcoholism, malignancy, liver
originally developed for the treatment of dyslipidemia. In addi- disease, chronic steroid use, infection with human immun-
tion to reducing atherosclerotic inflammation, these drugs may odeficiency virus, and ALI secondary to sepsis or aspiration
also reduce morbidity in other inflammatory conditions such [13,310]. Curiously, although patients of advanced age, par-
as rheumatoid arthritis [277], influenza [278], sepsis [279], ticularly older than 70 years, are at a significantly higher risk
and ALI [280]. The mechanisms through which statins are be- of death from ALI, those who survive recover at the same rate
lieved to provide benefit [281] include reduced expression of as their younger counterparts [311,312]. Chronic alcoholism
leukocyte and endothelial adhesion molecules [282,283], re- has been shown to not only increase the risk of developing
duced production of acute phase reactants (C-reactive protein) ALI in patient at risk [42], but to also increase the risk of de-
and inflammatory cytokines (IL-6, IL-8 and TNF-) [284,285], veloping multiorgan dysfunction after the development of ALI
and impaired coagulation via platelet stabilization [286], re- [40]. Plasma granulocyte colony stimulating factor (G-CSF)
duced TF and thrombin activity [287,288], and suppressed levels [313] and body-mass index (BMI) [314] both exhibit a
PAI-1 expression [289]. These drugs have also been shown to U-shaped distribution of relative risk for mortality in ALI, with
promote the mobilization of circulating EPCs [290]. There is higher risk falling on both the low and high ends of the curve.
experimental data from animal models of ALI arising from In the case of BMI, although it is somewhat intuitive that pa-
ischemia-reperfusion [291] and endotoxemia [280] demon- tients with either an exceedingly low or excessively high BMI
strating an amelioration of lung inflammation and vascu- would be at greater risk of death, investigators were somewhat
lar permeability associated with statin therapy. To date, the surprised to find the lowest risk belonging to those considered
only clinical data supporting statin use in ALI comes from a obese, with a BMI between 30 and 40 [314]. Investigators
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504 Section IV: Pulmonary Problems in the Intensive Care Unit

TA B L E 4 7 . 3
TABLE SUMMARIZING ALL RANDOMIZED TRIALS OF PHARMACOLOGIC TREATMENTS AND VENTILATION
STRATEGIES FOR ACUTE LUNG INJURY AND ACUTE RESPIRATORY DISTRESS SYNDROMEa

No. of
Intervention Year Study patients Findings Reference

High levels of positive 1975 Observational 28 High incidence of pneumothorax [300]


end-expiratory pressure
Extracorporeal membrane 1979 Phase 3 multicenter 90 No benefit [169]
oxygenation
High frequency ventilation 1983 Phase 3 multicenter 309 No benefit [301]
Preventative PEEP (8 cm H2 O) 1984 Phase 3 single center 92 No benefit in patients at risk of ALI [302]
Glucocorticoids (during acute 1987 Phase 3 87 No benefit [239]
phase)
Glucocorticoids (during acute 1988 Phase 3 59 No benefit [238]
phase)
Alprostadil: Intravenous 1989 Phase 3 100 No benefit [303]
Liposomal 1999 Phase 3 350 Stopped for lack of efficacy [304]
Extracorporeal membrane 1994 Phase 3 single center 40 No benefit [168]
oxygenation
Surfactant (aerosolized) 1996 Phase 3 725 No benefit [224]
Open-lung approach 1998 Phase 3 single center 53 Decreased 28-day but not [2]
(recruitment maneuver and in-hospital mortality
ideal PEEP)
Low tidal volume ventilation 1998 Phase 3 120 No benefit in patients at risk for [120]
(7 vs. 11 ml/kg) ALI/ARDS
Low tidal volume ventilation 1998 Phase 3 116 No benefit [118]
(7 vs. 10 mL/kg)
Glucocorticoids during late 1998 Phase 3 24 Decreased mortality, but study [240]
fibrosing alveolitis small
Inhaled nitric oxide 1998 Phase 2 177 No benefit [211]
Inhaled nitric oxide 1999 Phase 3 203 No benefit [305]
Ketoconazole 2000 Phase 2 234 No benefit [306]
Low tidal volumes (6 vs. 2000 Phase 3, multicenter 861 Decreased mortality from 40% to [1]
12 mL/kg) 30%
Prone positioning during 2001 Phase 3, multicenter 304 Improved oxygenation, but no [192]
mechanical ventilation benefit in mortality
Partial liquid ventilation 2002 Phase 3, multicenter 90 Lower progression to ARDS, but no [307]
benefit in mortality
Recombinant surfactant protein 2004 Phase 3, multicenter 448 Improved oxygenation at 24 hours [3]
C-based surfactant but no benefit in mortality
Prone positioning for hypoxemic 2004 Phase 3, multicenter 791 No benefit in 28 or 90 day mortality [194]
acute respiratory failure and some safety concerns
Higher versus lower PEEP 2004 Phase 3, multicenter 549 No benefit in mortality or days on [152]
during low tidal volume the ventilator
ventilation
Low and high dose partial liquid 2006 Phase 3, multicenter 311 No benefit in mortality and some [308]
ventilation safety concerns
Glucocorticoids for 2006 Phase 3, multicenter 180 No benefit in mortality; increased [242]
late/persistent ARDS mortality if started after 2 weeks
Conservative versus Liberal 2006 Phase 3, multicenter 1,000 No benefit in mortality; [200]
Fluid Management in ALI conservative strategy improved
lung function and reduced
ventilator days
Prolonged prone positioning for 2006 Phase 3, multicenter 136 Nonsignificant reduction in [193]
severe ALI mortality (43% vs. 58%,
p = 0.12)
Low tidal volumes, recruitment 2008 Phase 3, multicenter 983 No mortality benefit; less refractory [146]
maneuvers and high PEEP hypoxemia and rescue therapy
Low tidal volumes with plateau 2008 Phase 3, multicenter 767 No mortality benefit; higher organ [293]
pressure directed, high PEEP failure free and ventilator free
days and improved lung function
Activated Protein C 2008 Phase 2, multicenter 75 No benefit in ventilator-free days or [254]
mortality; reduced dead space

(continued)
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Chapter 47: Respiratory Failure Part II: Acute Respiratory Distress Syndrome 505

TA B L E 4 7 . 3
CONTINUED

No. of
Intervention Year Study patients Findings Reference

l-2-oxothiazolidine-4-carboxylic 2008 Phase 2, multicenter 215 Terminated early due to higher 30 day [309]
acid mortality & reduced vent-free days
Early mobilization in ICU for 2008 Multicenter 330 Decreased intensive care unit and [296]
patients with respiratory failure prospective hospital length of stay in survivors
Early physical therapy in ICU for 2009 Randomized, two 104 Decreased days on mechanical ventilation [297]
patients with respiratory failure centers and ICU length of stay; increased
functional independence at time of
discharge
Site-inactivated factor VIIa 2009 Phase 2, multicenter 46 Terminated early due to higher [256]
28 day mortality in high dose group
and trend toward increased bleeding
ECMO vs. conventional ventilatory 2009 Randomized 180 Reduced death or severe disability at [170]
support for severe adult multicenter 6 months
respiratory failure (CESAR)
Albuterol to treat acute lung injury 2009 Phase 2 and 3, 282 Terminated early due to projected futility [260]
(ALTA) multicenter by DSMB
Fish oil in patients with ALI 2009 Phase 2 multicenter 90 No difference in BALF IL-8 or LTB4 ; trend [265]
toward reduced ICU stay
Omega-3 fatty acids 2009 Phase 3, multicenter 272 Omega arm terminated early due to [266]
supplementation for ALI project futility
(EDEN-Omega)
Neuromuscular blockade in early 2010 Phase 3, multicenter 48 hours cisartacurium reduced mortality [338]
severe ARDS and increased ventilator-free days
without prolonged weakness
a
Results of randomized clinical trials of pharmacologic treatments and ventilatory strategies for acute lung injury and acute respiratory distress
syndrome.
Table partially adapted from Ware LB, Matthay MA: The acute respiratory distress syndrome. N Engl J Med 342:13341349, 2000, with updated
additions.

are also uncovering genetic polymorphisms and phenotypes A regimented sedation protocol designed to promote daily
among ALI patients that lead to an increased risk of mortal- awakenings and lower overall sedation in critically ill patients
ity. Individuals carrying specific haplotypes for IL-6 [315] or an was associated with decreased days in the ICU and fewer days
endogenous inhibitor of NF-kB [316] have an increased suscep- on mechanical ventilation [330]. Furthermore, to help raze the
tibility to ALI and mortality is increased in patients with ALI, myth that daily awakening be traumatic for patients, this strat-
with specific polymorphisms for surfactant protein B [317], egy has since been found to actually reduce PTSD-related symp-
pre-B-cell colony enhancing factor [318], or VEGF [319]. toms following recovery [331]. The feasibility and importance
of establishing clear sedation goals and using validated tools
for sedation assessment in critically ill patients has been firmly
Outcomes established [332,333], and this standard of care is now a part
of established professional society guidelines for sedation in the
Estimates of mortality from ALI once ranged as high as 70% ICU [334]. It remains to be seen whether these guidelines will
[110,320]. Despite a documented decline between the early be adapted to accommodate recent findings showing a reduc-
1980s and late 1990s [110,320], mortality from ALI appears tion in ARDS mortality with 48 hours of early neuromuscular
to have now plateaued between 30% and 40% for all patients, blockade [338].
[1,7,110,320]. As mortality has slowly improved for ALI, there
has been growing interest in the long range consequences of this
condition. In particular, ALI survivors have been shown to suf- CONCLUSION
fer from a prolonged disturbance in lung function [321,322],
an impairment in neurocognitive skills [323,324], and a per- Since its first published description in 1967 [213], our under-
ception of poor quality of life [324,325]. By as far out as one standing of the pathogenesis and pathophysiology of ALI has
year from recovery, although many have recovered spirometric grown appreciably, and ongoing research efforts continue to
lung function [326], the majority of ALI survivors have a di- provide hope for exciting new therapies in the future. Our im-
minished diffusing capacity and exercise tolerance [321,326]. proved understanding of this condition has already translated
One report noted less than half of all ALI survivors returning into improved outcomes for patients suffering from ALI [320],
to work after 1 year [326], and many survivors suffer from de- but its still ominous prognosis for those acutely afflicted in
pression and anxiety as far as 2 years out from recovery [324]. the hospital [7], and those fortunate enough to survive [324],
In a recently published study, symptoms of moderate to severe leaves room for ongoing progress in the management of these
depression were reported by 41% of survivors within 6 to 48 patients. Aside from the obvious importance of reducing mor-
months following discharge [327]. Posttraumatic stress disor- tality from this condition, a reduction in days on the ventilator
der (PTSD) has been another growing concern among survivors and subsequent stay in the intensive care unit represent some
[328] and delusional memories of ICU stay have been shown of the other tangible and intangible benefits to both patients
to correlate with the development of PTSD symptoms [329]. and society in general [335,336].
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506 Section IV: Pulmonary Problems in the Intensive Care Unit

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512 Section IV: Pulmonary Problems in the Intensive Care Unit

CHAPTER 48 RESPIRATORY FAILURE


PART III: ASTHMA
J. MARK MADISON AND RICHARD S. IRWIN

Asthma is an inflammatory disease of the airways characterized disparities and this suggests that prehospitalization factors are
by reversible airway obstruction [1,2]. Inflammation causes air- more important [12].
way obstruction by making airway smooth muscle more sen-
sitive to contractile stimuli [3], by thickening the airway wall
with edema and inflammatory cell infiltration, by stimulating PATHOPHYSIOLOGY
glands to secrete mucus into the airway lumen, by damaging
the airway epithelium [4], and by remodeling the architecture
of the airways [5]. Typically, intermittent worsening or exac- Pathology
erbation of asthma is triggered by exposure to environmental
factors such as inhaled allergens, irritants, or viral infections Bronchial biopsy specimens of patients with asthma are patho-
of the respiratory tract. These exacerbations represent acute logically abnormal [1315], with collagen deposition beneath
or subacute episodes of increased airflow obstruction that may the epithelial basement membranes, mucosal infiltration by
be mild to life threatening in severity. Assessment, manage- eosinophils and neutrophils, mast cell degranulation, and ep-
ment, and prevention of exacerbations of asthma, especially ithelial damage. These findings occur in both severe and mild
those leading to respiratory failure, are the critical challenges asthma, suggesting that airway inflammation is of primary im-
of caring for adult patients with asthma [6,7], the focus of this portance in the pathogenesis of asthma.
chapter. Asthma exacerbations show variable pathology, reflecting
at least two recognized subtypes of exacerbationslow onset
and rapid onset. Slow onset exacerbations are the most com-
mon (approximately 80% of exacerbations) and the patient
EPIDEMIOLOGY presents with more than 2 to 6 hours of symptomsoften days
or weeks of symptoms [1618]. This suggests that most such
Worldwide, asthma ranks among the most common chronic patients should have sufficient time to seek medical attention
diseases, with a prevalence ranging from a low of 0.7% in for worsening shortness of breath [19]. At autopsy, the lungs
Macau, 6.7% in Japan, 10.9% in the United States, and a high of patients who die of slow-onset asthma exacerbations are
of 18.4% in Scotland [8]. In general, asthma prevalence in- hyperinflated with thick tenacious mucus filling and obstruct-
creases with urbanization and westernization of societies. In ing the lumens of the airways [4]. Microscopically, there is
the United States, from 1980 to 1996, self-reported asthma an eosinophilic bronchitis, with pronounced areas of mucosal
prevalence increased 73.9% but then stabilized from 1997 to edema and desquamation of the epithelium. Typically, hyper-
2004 [9]. trophy and hyperplasia of smooth muscle are present and the
Asthma exacerbation rates vary by season with peaks in muscle appears contracted [4].
emergency room visits and hospitalizations coinciding with res- The patient with the rapid-onset type of exacerbation
piratory viral infections, especially rhinovirus, in late summer presents with severe symptoms that have rapidly progressed
and early autumn [10]. In 2002, annual rates of hospitalization over 2 to 6 hours [1618]. These rapid-onset exacerbations
for asthma in the United States were 27 per 10,000 population- may represent 8% to 14% of asthma exacerbations in general
age 017 years and 13 per 10,000 population-age 18 and over. and can be fatal, leading to death in only a few hours after
Although there remain important racial and gender differences symptom onset [16,18]. Pathologically, airway obstruction by
in the rates of hospitalization, this represents an overall de- mucus is not prominent, and there is a neutrophil, rather than
cline in hospitalizations from 1995 to 2002 and this suggests eosinophil, predominance of inflammatory cells in the airway
the possibility of better management and prevention of asthma submucosa [20]. There are no specific clinical characteristics
exacerbations in ambulatory settings over these years [11]. that reliably predict which patients are prone to these rapid-
In 2002 there were 4,261 deaths due to asthma in the United onset asthma exacerbations. However, patients with rapid on-
States indicating a death rate of 1.5 per 100,000 population of set asthma exacerbations may more commonly report sensitiv-
all ages [9]. Asthma mortality rates also have an annual cy- ity to nonsteroidal anti-inflammatory drugs (NSAIDs) [18].
cle, but do not strictly parallel the cycle for exacerbations. In
children, mortality peaks in the summer months, but, with in-
creasing age, asthma mortality becomes more common in win- Pathogenesis
ter months [10]. In 2002, the death rate for ages 18 years and
older was 1.9 deaths per 100,000 population, but it is notable Asthma is a disease or group of diseases with complex under-
that there are very large racial differences in the risk of death lying genetics [21]. Why airway inflammation develops in the
due to asthma. Blacks aged 25 to 34 years are six times more asthmatic patient is not understood entirely, but much evidence
likely to die from asthma than whites of the same age group [9]. suggests an important role for Th2 cytokines [22]. Inhaled al-
Deaths among patients hospitalized for asthma do account for lergens, pollutants, smoke, and viral infections all may play a
one third of asthma related mortality, but potential differences role in augmenting the baseline airway inflammation present
in hospital care do not appear to account for the striking racial in the asthmatic airway [1,23]. When these environmental
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Chapter 48: Respiratory Failure Part III: Asthma 513

triggers interact with the asthmatic airway, the inflammation TA B L E 4 8 . 1


is intensified and the released mediators have potent effects on
smooth muscle cell function, epithelium and microvascular in- DIFFERENTIAL DIAGNOSIS OF WHEEZING
tegrity, neural function, and mucus gland secretion. All these
factors contribute to increased narrowing of the asthmatic air- Upper airway obstruction
way with smooth muscle contraction, mucus secretion, epithe- Extrathoracic
lial cell sloughing into the lumen, and edema and inflammatory Anaphylaxis
cell infiltration of the airway wall. The resulting acute increase Arytenoid dysfunction
in airway obstruction is commonly referred to as an acute ex- Bilateral vocal cord paralysis
acerbation of asthma. Laryngeal edema
Laryngostenosis
Laryngocele
Mobile supraglottic soft tissue
Physiology Neoplasms
Postextubation granuloma
The major physiologic consequences of airway obstruction are Postnasal drip syndrome
hypoxemia and increased work of breathing. Understanding Relapsing polychondritis
these physiologic disturbances is important for management Retropharyngeal abscess
of severe exacerbations of asthma. Supraglottitis
Narrowing the caliber of airway lumens causes hypoxemia Vocal cord dysfunction syndrome
by two mechanisms. First, increases in the resistance to flow in Wegener granulomatosis
the conducting airways result in uneven distribution of venti- Intrathoracic
lation to the alveoli. Hypoxic vasoconstriction of vessels that Acquired tracheomalacia
supply underventilated alveoli partially compensates for this Airway neoplasms
Q)
uneven ventilation, but overall ventilationperfusion (V/ ra-
Foreign body aspiration
tios remain abnormal and are the principal cause of hypoxemia Goiter
in asthma [24]. Consequently, even patients with severe exac- Herpetic tracheobronchitis
erbations of asthma usually respond well to supplemental oxy- Right-side aortic arch
gen. A second, less common cause of hypoxemia in asthma is Tracheal stenosis due to intubation
right-to-left shunt due to atelectasis of lung distal to airways Tracheobronchomegaly
that are completely occluded by mucus or due to interatrial
shunt [2527]. Lower airway obstruction
The second physiologic consequence of severe airway ob- Aspiration
struction is increased work of breathing. During acute exac- Asthma
erbations, respiratory muscles must expend increased energy, Bronchiectasis
generating large changes in pleural pressure to overcome high Bronchiolitis
airway resistance [28]. The resulting discordance between res- Carcinoid syndrome
piratory effort and the change in thoracic volume also plays Chronic obstructive pulmonary disease
a role in the patients sensation of dyspnea and central drive Cystic fibrosis
to increase minute ventilation. The ensuing rapid respirations Lymphangitic carcinomatosis
further increase the work of breathing and worsen air trapping Pulmonary edema
behind narrowed airways that prematurely close during expi- Parasitic infections
ration. The dynamic hyperinflation of the lung itself leads to Pulmonary embolism
increased respiratory muscle energy costs because it restricts
vital capacity to high thoracic volumes where alveolar dead
space is increased, the respiratory muscles are at suboptimal
mechanical advantage, and the lung is less compliant. All of ence, extrathoracic variable obstruction on flow-volume loop,
these factors contribute to the enormous increase in the work and observing paradoxic closure of vocal cords during inspira-
of breathing. Thus, the respiratory muscles must expend more tion on laryngoscopy.
energy to achieve the same alveolar ventilation. Initially, the Furthermore, many disease processes other than asthma can
respiratory muscles may be able to exert the force needed to obstruct the lower airways to produce wheezing and dysp-
maintain alveolar ventilation but the muscles may fatigue if nea (Table 48.1). Systemic anaphylaxis can cause wheezing
airway resistance increases rapidly, is sustained, or if there is and should be considered in the differential diagnosis espe-
inadequate oxygen delivery to theses muscles [29,30]. Dynamic cially when respiratory symptoms have been of rapid onset
hyperinflation due to severe airway obstruction also may im- and progress [36]. A diagnosis of anaphylaxis is suggested by
pair cardiac performance by increasing afterload, decreasing acute-onset wheezing, stridor, urticaria, nausea, diarrhea, and
venous return to the heart, and causing diastolic dysfunction hypotension (especially after insect bites, drug administration,
[7,27]. or intravenous contrast). Exacerbations of chronic obstructive
pulmonary disease (COPD) present similarly to acute asthma,
but chronic bronchitis or emphysema, or both, can usually
be distinguished from asthma historically. Pulmonary throm-
DIFFERENTIAL DIAGNOSIS boembolism can masquerade as an exacerbation of asthma
because the mediators released by platelets in thromboemboli
Not all wheezing is due to asthma (Table 48.1). Obstruction of sometimes cause bronchoconstriction and wheezing. However,
the airway at any level can produce wheezing and dyspnea that hemoptysis, pleuritic pain, and pleural effusions rarely are seen
can be confused with asthma. For example, vocal cord dysfunc- in acute exacerbations of asthma.
tion syndrome [3135] is an extrathoracic cause of upper air- Pulmonary edema, either cardiogenic or noncardiogenic,
way obstruction that can be confused with acute asthma. This can obstruct small airways with mucosal swelling to produce
diagnosis is suggested by the presence of stridor and wheeze in acute wheezing. However, in these cases the clinical history,
the absence of increased alveolar-arterial oxygen tension differ- physical examination, and chest radiograph changes that show
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514 Section IV: Pulmonary Problems in the Intensive Care Unit

vascular redistribution of blood flow and alveolar filling help paradoxus greater than 10 mm Hg, and accessory respiratory
exclude asthma as a diagnosis. Notably, however, acute, re- muscle use all should be regarded as signs of severe airway
versible left ventricular dysfunction has been described as a obstruction [52]. However, because the absence of these signs
possible complication of severe exacerbations of asthma; the does not rule out severe obstruction, physical examination can-
underlying mechanism for this is unclear [37]. Aspiration can not be relied on exclusively to estimate the severity of airway
present with acute dyspnea and wheezing. In this case, a his- obstruction. The amount of wheezing heard on auscultation of
tory of impaired consciousness or inability to protect the air- the chest is a notoriously poor method of assessing the severity
way suggests that the diagnosis and chest radiograph may show of airway obstruction [53]. Cyanosis is a late, insensitive find-
pulmonary infiltration. ing of severe hypoxemia. Abnormal thoracoabdominal motion
(e.g., respiratory muscle alternans, abdominal paradox) and
depressed mental status due to hypoxemia and hypercapnia are
ASSESSMENT ominous indicators and can herald the necessity for mechanical
ventilation [54].
Physician failure to appreciate the severity of airway obstruc-
tion in acute asthma is not uncommon and contributes to
mortality [1]. The cornerstone of evaluation of patients with Pulmonary Function Tests
asthma exacerbations is the objective measurement of airflow.
However, because some patients, especially those with severe To evaluate patients who are having an acute exacerbation of
exacerbations, may be unable to perform the necessary test- asthma, an objective measure of maximal expiratory airflow
ing maneuvers, the physician also must be adept at recognizing should be performed. An exception to this is the patient who
certain historical features and physical findings that strongly is unable to perform a testing maneuver due to a severe, life-
suggest high risk for severe airway obstruction. threatening exacerbation with obvious airway compromise and
cyanosis [44]. Peak expiratory airflow rate (PEFR) and FEV1
are equally good bedside measures to quantify the degree of
History airway obstruction [55]. These tests are invaluable for the ini-
tial assessment and for following responses to therapy [44,56].
Baseline pulmonary function tests that show persistent de- In general, a PEFR or FEV1 of less than 40% of baseline (either
creases in the forced expired volume of air in 1 second (FEV1 ), the predicted value or the patients best-known value) indicates
loss of lung elastic recoil, and hyperinflation at total lung ca- severe obstruction and a severe exacerbation of asthma (Table
pacity are associated with increased risk of near-fatal asthma 48.2).
[38]. A recent history of poorly controlled asthma (increases
in dyspnea and wheezing, frequent nocturnal awakenings due
to shortness of breath, increased use of beta-adrenergic res-
cue medications, increased diurnal variability in peak expira- Arterial Blood Gas Analysis
tory flow, and recent hospitalizations or emergency department
Analysis of arterial blood gases (ABGs) have a role in assess-
visits) and any history of a prior near-fatal asthma exacerba-
ing and managing severe asthma exacerbations (see Chapter
tion (prior admission to an intensive care unit or intubation
11) and should be performed for suspected hypoventilation,
for asthma) are the two most important predictors of a pa-
severe respiratory distress, or when spirometric test results are
tients propensity for severe life-threatening asthma exacerba-
less than 25% predicted [44]. Also, any patient who fails to
tions [3944]. Patient complaints of severe breathlessness or
respond to the first 30 to 60 minutes of intensive bronchodila-
chest tightness or difficulty walking more than 100 feet (30.48
tor therapy should have an ABG analysis performed. Although
m) also suggest severe airway obstruction. Cigarette smoking
ABG values are not predictive of overall patient outcome [55],
also has been associated with higher in-hospital and posthos-
there is some correlation between hypoxemia and hypercapnia
pitalization mortality [43]. In general, patients are somewhat
and the degree of airway obstruction measured by FEV1 [57]. A
better judges of the severity of their airway obstruction during
partial pressure of arterial oxygen (PaO2 ) less than 60 mm Hg
an attack of asthma than are physicians who elicit their history
or a pulse oximeter oxygen saturation value less than 90% on
at the bedside [45]. However, the patients own assessment of
room air should be regarded as additional evidence of severe
airway obstruction should never be the exclusive means of as-
airway obstruction. Therefore, although ABG analysis is not
sessing the severity of airway obstruction. Notably, patients
recommended as routine in the initial evaluation of asthma, it
with a history of severe asthma often have a blunted percep-
should be done for the evaluation of severe cases. One study
tion of dyspnea [4649]. In assessing risk for fatal asthma,
found that the frequency of ABG analysis in cases of severe
other important historical details include identification of cur-
asthma actually decreased from 1997 to 2000, a trend needing
rent medications and coexisting illnesses, such as psychiatric
improvement [58].
disease, that interfere with medical follow-up and cardiopul-
monary disease. A history of known coronary artery disease
is important because the patient may be more sensitive to the
stimulatory effects of 2 -adrenergic agonists and to the cardiac TA B L E 4 8 . 2
complications of hypoxemia [50]. These patients may also be
receiving 2 -adrenergic antagonists that are making control of OBJECTIVE ASSESSMENT OF AIRWAY OBSTRUCTION
their asthma worse. AFTER INITIAL INTENSIVE THERAPY

PEFR or FEV1 Interpretation


Physical Examination 70% predicted Good response
40% but 69% predicted Incomplete response
Physical examination is important for excluding other causes of
<40% predicted Poor response
dyspnea (see Differential Diagnosis section) and assessing the
degree of airway obstruction [44]. Tachycardia (greater than FEV1 , forced expired volume in 1 second; PEFR, peak expiratory flow
120 beats per minute), tachypnea (greater than 30 breaths per rate.
minute), diaphoresis [51], bolt-upright posture in bed, pulsus
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Chapter 48: Respiratory Failure Part III: Asthma 515

Understanding the expected changes in the partial pressure TA B L E 4 8 . 3


of arterial carbon dioxide (PaCO2 ) during an asthma exacer-
bation is important for recognition of a rapidly deteriorating TREATMENT OF SEVERE ACUTE EXACERBATIONS
course. With modest airway obstruction, the patients mild dys- OF ASTHMA
pnea stimulates an increase in minute ventilation that meets or
exceeds the level required to maintain normal alveolar ventila- Pharmacologic agents
tion. Thus, patients with modest obstruction have a normal or Anti-inflammatory agents
slightly below normal PaCO2 . As airway obstruction worsens, Systemic corticosteroids (oral preferred unless impaired
dyspnea becomes more severe and the central nervous system intestinal absorption)
drive to increase minute ventilation becomes intense. Typically, Bronchodilators
the increase in minute ventilation exceeds the level required to Inhaled 2 -adrenergic agonists
maintain constant alveolar ventilation; consequently, patients Inhaled cholinergic antagonists
with moderate-to-severe obstruction have lower than normal MgSO4 (not routine; consider in severe, refractory cases)
PaCO2 and respiratory alkalosis. As the airway obstruction Oral or intravenous methylxanthines (not routine or
becomes more severe and prolonged, high minute ventilation recommended)
can no longer be maintained by the respiratory musculature Systemic 2 -adrenergic agonists (not routine or
and alveolar ventilation decreases. As a result, the PaCO2 rises recommended)
toward normal and then continues to climb, resulting in hy- General anesthetics (not routine)
percapnia and respiratory acidosis. Thus, a normal or high Supportive measures
PaCO2 (greater than 40 mm Hg) during a severe exacerbation Frequent reassessment
of asthma is a potentially ominous finding, often signifying Supplemental oxygen
the impending need for mechanical ventilation. Any coexisting Fluid management
conditions (malnutrition, advanced age) or medications (seda- Invasive mechanical ventilation if needed (controlled
tives) that weaken respiratory muscle function or depress res- hypoventilation)
piratory drive should be expected to accelerate the onset of Helium-oxygen mixtures to drive nebulizer (not routine;
hypercapnic ventilatory failure during acute exacerbations of consider in severe, refractory cases)
asthma. Lavage by bronchoscopy (not routine, intubated patients
only)
Education
Other Laboratory Studies Avoidance of asthma triggers
Medication use
For acute exacerbations of asthma, routine chest radiographs
Access to medical follow-up
reveal few abnormalities other than hyperinflation [59]. How-
Home monitoring of airway obstruction
ever, although not recommended for routine assessment, for se-
vere exacerbations chest radiography can be helpful when there
is clinical suspicion of other causes of dyspnea and wheezing
(see Differential Diagnosis section) or complications of severe
airway obstruction [44]. Chest radiographs should be exam- therapy with systemic corticosteroids [61]. Because corticos-
ined for evidence of enlarged cardiac silhouette, upper lung teroids take at least 4 to 6 hours to begin to have a beneficial
zone redistribution of blood flow, pleural effusions, and alve- effect and the inflammatory causes of airway obstruction may
olar or interstitial infiltrates because any one of these findings take days to resolve, the medical challenge is to support patients
suggests a diagnosis other than or in addition to acute asthma. until the inflammatory processes have responded to corticos-
In addition, chest radiography allows the early detection of teroids.
common complications of severe airway obstruction, includ- 2 -Adrenergic agonists relieve airway obstruction due to
ing pneumothorax, pneumomediastinum, and atelectasis. Also, airway smooth muscle contraction, and this is an impor-
lung infiltrates on chest radiographs can be compatible with a tant therapeutic maneuver in initial treatment. Although these
diagnosis of asthma complicated by either allergic bronchopul- bronchodilators relieve only one component of the airway ob-
monary aspergillosis or ChurgStrauss syndrome. struction during severe exacerbations of asthma, even small
In the elderly, in patients with severe hypoxemia, and in in- improvements in airflow can lead to important clinical bene-
dividuals with suspected cardiac ischemia or arrhythmia, an fits in the acute setting. Of the available bronchodilators, 2 -
electrocardiogram should be performed. Sinus tachycardia is adrenergic agonists are the most effective and rapidly acting
common during acute exacerbations of asthma, but less com- and, therefore, most useful during that critical time before the
mon and transient findings include right-axis deviation, right onset of corticosteroid action [62]. Other measures that sup-
ventricular hypertrophy and strain, P pulmonale, ST- and T- port the patient until the inflammatory processes in the airways
wave abnormalities, right bundle-branch block, and ventricu- have resolved include supplemental oxygen, judicious fluid ad-
lar ectopic beats [60]. ministration, and, when indicated, mechanical ventilation.

THERAPEUTIC AGENTS 2 -Adrenergic Agonists


Optimal management of an acute exacerbation of asthma be- 2 -Adrenergic agonists bind to 2 -adrenergic receptors on air-
gins with a careful assessment of the degree of airway obstruc- way smooth muscle cells and cause relaxation of the muscle
tion. This initial assessment and repeated objective measures cell. Although the primary cellular target of 2 -adrenergic ag-
of airway obstruction guide treatment that combines support- onists is airway smooth muscle, other cell types in the airways
ive measures, bronchodilator therapy, and anti-inflammatory also express 2 -adrenergic receptors that may regulate media-
therapy (Table 48.3). tor release by mast cells, epithelial cells, and nerves.
Because the dominant causes of airway obstruction during There are two general classes of 2 -adrenergic ago-
an acute exacerbation of asthma are the result of airway in- nists. Short-acting 2 -adrenergic agonists (SABA) have bron-
flammation, the cornerstone of treatment is anti-inflammatory chodilatory effects that last for 3 to 5 hours. They include
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516 Section IV: Pulmonary Problems in the Intensive Care Unit

epinephrine, isoproterenol, terbutaline, metaproterenol, al- breathing devices, and pneumothorax resulting in death has
buterol, and fenoterol. These short-acting agents have an onset been reported [78].
of action less than 5 minutes and are the mainstay of bron- Because of its lower density than oxygen, heliox-powered
chodilator therapy for acute asthma. These agents differ in nebulizer treatments have the potential to improve penetration
their selectivity for 2 -adrenergic receptors, the rank order of aerosols into the lungs. Adult patients with severe asthma
of selectivity being epinephrine < isoproterenol < metapro- exacerbations had greater improvements in peak expiratory
terenol < fenoterol, terbutaline, and albuterol [63]. However, flow rates and dyspnea scores when albuterol was delivered
all of these agents have approximately equal efficacy in the using heliox, rather than oxygen, driven nebulization [79,80].
treatment of asthma. Another class of drugs, the long-acting Current National Institute of Health Guidelines suggest that
2 -adrenergic agonists (LABA), have bronchodilatory effects heliox-driven albuterol nebulization be considered for patients
for at least 12 hours, but these agents are not currently rec- with life-threatening exacerbations or for those with severe
ommended in the treatment of acute exacerbations [1,2,44]. exacerbations even after 1 hour of intensive conventional
There has been significant controversy on whether chronic use therapy [1].
of these long-acting agents predisposes patients to increased Theoretically, systemic administration of beta-adrenergic
severe, life-threatening, or fatal asthma exacerbations [64]. agonists could deliver drugs via the bloodstream to obstructed
Among the short-acting 2 -adrenergic agonists, a single- airways that are poorly accessible to inhaled aerosols. How-
isomer preparation (i.e., R-albuterol or levalbuterol) is avail- ever, this theoretical advantage has not been supported by most
able. The potential advantage of this preparation is that the studies [71]. Subcutaneous epinephrine (adults, 0.3 mL of a 1
S-enantiomer present in racemic albuterol, does not contribute to 1,000 solution every 20 minutes for three doses) was a tradi-
to bronchodilation and might have deleterious effects in the tional therapy for acute asthma in emergency departments, but
airways. However, although some studies of levalbuterol (R- it is not more effective than aerosol delivery of 2 -adrenergic
albuterol) in the emergency department setting have suggested agonists [81]. A major concern with the use of subcutaneous
that levalbuterol is a more efficacious bronchodilator than epinephrine in adults has been cardiac toxicity [82]. More se-
racemic preparations, there have been no large, randomized, lective 2 -adrenergic agonists, such as terbutaline, are avail-
double-blind and controlled trials in adults to confirm these able for subcutaneous use, but cardiac toxicity in elderly in-
findings [6567]. dividuals is still a significant concern even with these more
The major side effects of 2 -adrenergic agonists during the selective agents. Formerly, intravenous isoproterenol (0.05 to
treatment of severe asthma exacerbations are tremor, cardiac 1.50 g per kg per minute) was often used to treat severe ex-
stimulation, and hypokalemia [68]. Case reports have associ- acerbations of asthma [83]. However, intravenous delivery of
ated lactic acidosis with the use of 2 -adrenergic agonists as 2 -adrenergic agonists is no longer recommended for the rou-
well [69]. These side effects are potentially serious, especially tine treatment of even severe exacerbations of asthma [1,2].
in the elderly, who frequently have underlying cardiac disease. No convincing evidence has shown intravenous administration
Cardiac toxicity can be minimized by using agonists with high to be superior to inhaled delivery of 2 -adrenergic agonists.
2 -adrenergic receptor selectivity, by avoiding systemic admin- The lack of enhanced efficacy and the potential cardiac tox-
istration of 2 -adrenergic agonists, and by maintaining ade- icity of intravenous 2 -adrenergic agonists have led most au-
quate oxygenation [50,70]. thorities to reserve intravenous delivery for those rare patients
2 -Adrenergic agonists can be administered to patients by who continue to deteriorate on mechanical ventilation despite
inhaled, subcutaneous, or intravenous routes. Numerous stud- maximal routine therapy with inhaled 2 -adrenergic agonists
ies have shown that the bronchodilator effects of inhaled 2 - [83]. Intravenous 2 -adrenergic agonists should be used only
adrenergic agonists are rapid in onset and equal to the effect in closely monitored adults because myocardial ischemia can
achieved by systemic delivery [71]. Because the inhaled route occur [84]. It is important to emphasize again that intravenous
allows administration of comparatively small doses directly to 2 -adrenergic agonists are not recommended in current NIH
the airways with minimal systemic toxicity, this route is almost guidelines and are unlikely to be any more effective than in-
always preferable to systemic delivery [1,2]. haled 2 -adrenergic agonists such as albuterol [1].
Several options exist for the delivery of inhaled 2 -
adrenergic agonists (see Chapter 62). A small-volume
nebulizer is widely used. However, studies have shown that Cholinergic Antagonists
metered-dose inhalers (MDIs) equipped with spacer devices
are as effective as small-volume nebulizers in the treatment The muscarinic cholinergic antagonists (e.g., atropine, ipra-
of acute asthma, although some patients may have difficulty tropium and tiotropium) are less effective and more slowly
coordinating MDI use, especially during an acute exacerba- acting bronchodilators than 2 -adrenergic agonists [8587].
tion with severe respiratory distress [1,72,73]. Frequent, mul- In general, these agents should not be used as the sole
tiple inhalations of the medication may allow for progressively bronchodilator therapy for acute asthma. Exceptions may be
deeper penetration of the drug into peripheral airways [74]. bronchospasm induced by acetylcholinesterase inhibitors or
In fact, continuous administration by nebulizer may be more 2 -adrenergic antagonists and patients with severe cardiac dis-
effective in severely obstructed patients [75,76]. For adminis- ease who are unable to tolerate 2 -adrenergic agonists.
tration of inhaled albuterol in the treatment of severe exac- However, inhaled cholinergic antagonists have a low in-
erbations of asthma, National Institutes of Health guidelines cidence of side effects and are a recommended adjunct to
recommend treatment with MDI (90 g per puff; four to eight 2 -adrenergic agonists in the initial emergency department
puffs every 20 minutes up to 4 hours, then every 1 to 4 hours treatment of severe exacerbations of asthma [1,88]. Because
as needed) or nebulizer treatments, either intermittent (2.5 to even small improvements in airflow could prove clinically sig-
5.0 mg every 20 minutes for 3 doses, then every 1 to 4 hours nificant in the severely obstructed and deteriorating patient, it
as needed) or continuous (10 to 15 mg per hour) [1] (see Man- is recommended that ipratropium be routinely added to 2 -
agement section). adrenergic agonist therapy during the initial treatment of se-
Intermittent positive-pressure breathing devices to deliver vere asthma exacerbations in the emergency department [1]
aerosols were once popular but are not used today because (see Management section). However, although comparable tri-
many patients with severe asthma cannot tolerate the device als for adults do not exist, controlled trials in children have
and because the devices are no more effective than small- not shown a benefit of continuing ipratropium treatment once
volume nebulizers [77]. Furthermore, the risk of barotrauma the patient is hospitalized [89,90]. Therefore, inhaled iprat-
is significantly increased with intermittent positive-pressure ropium bromide currently is not recommended for hospitalized
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Chapter 48: Respiratory Failure Part III: Asthma 517

patients with severe exacerbations of asthma [1]. The long- effectively prevent relapses of asthma after discharge from the
acting anticholinergic, tiotropium, has a role in treating out- emergency room [1,2,102,103]. Inhaled corticosteroids may
patients with difficult to control asthma, but whether it has a have topical effects that rapidly (less than 3 hours) vasocon-
role in treating hospitalized patients with acute exacerbations strict bronchial mucosal blood vessels and this could be one
of asthma is not yet known [91]. rapid mechanism of relieving airway obstruction, at least par-
tially [104].
The optimum dosages of corticosteroids for the treatment
Methylxanthines of acute asthma are not well established by randomized con-
trolled clinical trials either [1,2,61,105]. One study compared
Because the literature does not demonstrate a benefit to adding 15, 40, and 125 mg methylprednisolone every 6 hours and
methylxanthines to 2 -adrenergic agonists in the acute setting suggested that patients improved most rapidly with the 125-
[92,93] and because they increase toxicity [92], methylxan- mg dose [106]. However, most studies have failed to show a
thines are no longer recommended in the treatment of asthma dose-response relationship for doses this high [105]. For exam-
exacerbations [1]. Whether newer, less toxic, subtype selective ple, one study showed no difference between 100 and 500 mg
phosphodiesterase inhibitors have a role in the management of methylprednisolone in the emergency department treatment of
acute asthma exacerbations remains to be studied. asthma [107].
For rare patients whose condition is deteriorating despite For adults, NIH guidelines recommend that prednisone,
maximal routine recommended therapy with bronchodilators, methylprednisolone or prednisolone all be given at 40 to 80
corticosteroids and other adjuncts [1], the use of methylxan- mg per day in one or two divided doses until PEFR is 70%
thines might be considered by some physicians. For patients of predicted or personal best [1]. GINA guidelines describe
not already taking methylxanthines, a loading dose of amino- appropriate dosing as the equivalent of 6080 mg of methyl-
phylline (6 mg per kg lean body weight) can be administered prednisolone as a single daily dose, with 40 mg of methylpred-
during 20 to 30 minutes, followed by an intravenous infusion nisolone being adequate in most cases [2]. According to NIH
at the rate of 0.6 mg per kg per hour. This infusion rate should guidelines the duration of systemic corticosteroid treatment for
be decreased if conditions are present that decrease methylx- a patient requiring an emergency department visit or a hospi-
anthine clearance, especially congestive heart failure, cirrhosis, talization is usually 3 to 10 days [1]. GINA guidelines recom-
and the use of cimetidine, ranitidine, allopurinol, oral contra- mend a 7-day course for adults [2]. For courses lasting less than
ceptives, erythromycin, ciprofloxacin, or norfloxacin. Six hours 1 week and for treatment courses lasting up to 10 days, there
after initiation of the infusion, the serum theophylline level is no established benefit to slowly tapering the daily oral cor-
should be checked and the infusion rate adjusted accordingly, ticosteroid dose, especially if the patient is also using inhaled
with 10 to 15 g per mL being therapeutic. Serum concentra- corticosteroids [1,2,61].
tions greater than 20 g per mL are toxic.

Oxygen
Corticosteroids
Supplemental oxygen therapy should be the initial intervention
Numerous studies have documented the safety and effective- in the emergency department [1,2]. Because V/ Q mismatch is
ness of short courses of corticosteroids in the treatment of the dominant cause of hypoxemia in asthma, the PaO2 usually
acute exacerbations of asthma [1,2,61,9496]. Their beneficial increases readily in response to low levels (2 to 4 L per minute
effects are attributed to their many potent anti-inflammatory oxygen by nasal prongs) of supplemental oxygen therapy. In ad-
effects on multiple cell types [97]. Corticosteroids inhibit in- dition to mitigating the cardiac and neurologic complications
flammatory cytokine release by macrophages and T cells; de- of severe hypoxemia, low-flow supplemental oxygen minimizes
crease expression of endothelial cell adhesion molecules to in- potential episodes of hypoxemia due to the acute administra-
hibit migration of inflammatory cells into the airway; increase tion of 2 -adrenergic agonists, decreases elevated pulmonary
neutral endopeptidase expression to enhance degradation of vascular pressures due to hypoxic vasoconstriction, decreases
neuropeptides that regulate inflammation; decrease mast cells, bronchospasm due to hypoxia, and improves oxygen delivery
eosinophils, and CD4+ T lymphocytes in the airway submu- to respiratory muscles. Although low-flow oxygen is beneficial,
cosa; and decrease secretions from gland cells [97]. the routine use of 100% oxygen to treat acute asthma should be
Systemic corticosteroids are the principal therapy for acute avoided because this is usually not necessary and some evidence
exacerbations of asthma [1,2,61]. Prednisone, prednisolone, suggests that it may cause carbon dioxide retention [108].
and methylprednisolone are the preferred agents. Compared
with betamethasone and dexamethasone, neither prednisone
nor methylprednisolone contain metabisulfites and both have
shorter half-lives. Although hydrocortisone has the shortest Fluids
half-life, it has greater mineralocorticoid effect and may cause
idiosyncratic bronchospasm in some aspirin-sensitive individ- No convincing evidence has shown that fluid administration in
uals [98]. excess of euvolemia hastens mobilization of inspissated secre-
The optimal route of corticosteroid administration in the tions in the airways [1]. Fluid therapy should be used conser-
treatment of acute asthma is not well established by double- vatively unless significant dehydration is present.
blind, placebo-controlled clinical studies. For initial treatment
of an acute exacerbation of asthma, several studies suggest that
oral administration of corticosteroids is as effective as intra- Other Agents
venous therapy [1,2,61,99,100]. The oral route is preferred
unless there is the possibility of impaired gastrointestinal tract Intravenous magnesium sulfate (for adults, 2 g MgSO4 in
transit time or absorption [1,2]. 50 mL saline during 20 minutes) has bronchodilator proper-
Currently, inhaled corticosteroids do not have a well- ties and it has been recommended that emergency department
established role in the treatment of acute exacerbations of physicians consider its use in the treatment of severe asthma
asthma in hospitalized patients [1,2,61,101]. However, mount- exacerbations [1,2]. The NIH guidelines recommend that it be
ing evidence suggests that inhaled corticosteroids are an ef- used as adjunct treatment only in life-threatening exacerbations
fective addition to albuterol in the acute setting and they and in cases refractory to initial intensive conventional therapy
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518 Section IV: Pulmonary Problems in the Intensive Care Unit

because it may sometimes help to avoid intubation. Although published guidelines for the assessment and management of pa-
no major adverse events have been associated with MgSO4 in tients with acute exacerbations of asthma [1]. These guidelines
this setting, guidelines do not recommend its routine use in have been widely accepted and we recommend them. Initial
the treatment of severe acute asthma exacerbations in general management of a patient with an acute exacerbation of asthma
because results of meta-analyses remain mixed [1,2,109111]. is based on the physicians assessment of the degree of airway
Additional study is needed, but some evidence suggests that obstruction and the patients response to initial bronchodilator
its use may reduce hospitalization rates in the most severely therapy using 2 -adrenergic agonists. If, in the initial assess-
obstructed patients who have an FEV1 less than 25% of pre- ment, the patient is in extreme distress and has evidence of fa-
dicted [112]. Inhaled, rather than intravenous, magnesium sul- tigue, impaired consciousness, or hypercapnia such that respi-
fate may also have a role in the treatment of acute asthma. ratory arrest is judged imminent, endotracheal intubation and
That is, there is some evidence to suggest that albuterol neb- mechanical ventilation should be the first priorities and then
ulized in magnesium sulfate solution may be a more effective systemic corticosteroids and nebulized 2 -adrenergic agonists
bronchodilator than albuterol nebulized in normal saline [113]. and ipratropium should be started immediately. On the other
Neither GINA nor NIH asthma guidelines recommend hand, if respiratory arrest is not impending within minutes, 2
heliumoxygen therapy for routine treatment of acute asthma to 4 L per minute of supplemental oxygen should be initiated
exacerbations [1,2]. Some improvement in airway resistance to keep oxygen saturation greater than 90%; 2 -adrenergic ag-
may be achieved by delivering a mixture of helium and oxygen onists should be delivered by aerosol for three doses over 60
gases (heliox) to patients, but its role in the routine treatment to 90 minutes (e.g., albuterol, 2.5 to 5.0 mg, every 20 min-
of acute asthma remains unestablished [114,115]. However, utes by small-volume nebulizer for 3 doses, then 2.5 to 10 mg
other evidence does support a different role for heliox in the every 1 to 4 hours as needed, or 10 to 15 mg per hour contin-
treatment of acute asthma and that is to improve the delivery uously or, alternatively, albuterol, 90 g per puff, four to eight
of inhaled beta-adrenergic agonists, such as albuterol [79,80]. puffs by MDI with spacer every 20 minutes up to 4 hours, then
Current NIH guidelines suggest that heliox-driven albuterol every 1 to 4 hours as needed). If the PEFR is less than 50%
nebulization be considered for life-threatening exacerbations of the predicted value, an oral systemic corticosteroid should
or those exacerbations refractory to intensive conventional be started immediately and an inhaled anticholinergic as well
therapy [1]. (e.g., ipratropium bromide, 0.5 mg by nebulizer every 20 min-
Some therapeutic agents that are used in the treatment of utes for three doses and then every 2 to 4 hours as needed).
stable asthma have no established role in the treatment of se- After these treatments are initiated, a more detailed history and
vere exacerbations of asthma in hospitalized patients. These physical and laboratory examination can be completed. Close
include aerosolized corticosteroids and sodium cromolyn as monitoring and repeated airflow measurements are critical for
well as oral 2 -adrenergic agonists, which may cause signifi- detecting further deterioration during this initial period of
cant systemic toxicities. Although there is as yet no established treatment.
role for the use of leukotriene antagonists in the treatment of After the initial treatment with a bronchodilator, patients
acute asthma exacerbations, some evidence suggests a possible are reassessed. Those who do not respond substantially (FEV1
role and need for further study [116]. Mucus is an impor- or PEFR greater than 70% of predicted) within 1 hour to initial
tant cause of airway obstruction in acute exacerbations of treatment with 2 -adrenergic agonists should be given systemic
asthma, but the routine use of mucolytics, such as acetylcys- corticosteroids (if not already given). Oral prednisone is gener-
teine, potassium iodide, or human recombinant deoxyribonu- ally recommended unless there is concern that gastrointestinal
clease (DNase), has not been shown to be effective in treating tract absorption will be less than optimal [1,2].
severe exacerbations of asthma, and at least one of these agents, In addition to corticosteroids, treatment with 2 -adrenergic
acetylcysteine, may worsen cough and bronchospasm [117]. agonists and inhaled anticholinergics is continued for 1 to
However, it is notable that acetylcysteine and DNase may be 3 hours with frequent reassessment. Patients who achieve an
helpful during therapeutic bronchoscopy (see Additional and FEV1 or PEFR of greater than 70% during this 1- to 3-hour pe-
Unconventional Management Measures section). riod should be observed for at least 1 additional hour to ensure
Bacterial infections appear to play, at most, a minor role in stability of the improvement. In one study, two thirds of pa-
the precipitation of severe asthma exacerbations [1,2,118]; for tients who presented to the emergency department responded
this reason, antibiotics are not routinely administered unless an to albuterol, with the FEV1 increasing to at least 60% of pre-
active bacterial infectious process, particularly pneumonia and dicted [121]. Most patients with such a good response do not
bacterial sinusitis, is suspected. However, intriguing evidence require hospitalization. Exceptions are patients with a history
suggests that infections due to Mycoplasma pneumoniae [119] that is suggestive of high risk for mortality from asthma (e.g.,
or Chlamydia pneumoniae [120] might play an important role history of intubation and mechanical ventilation; Table 48.4).
in the pathogenesis of asthma and could be a precipitant of Patients discharged from the emergency department should be
asthma exacerbations. Further work is needed to resolve this continued on systemic corticosteroids and 2 -adrenergic ago-
important issue. nists, considered for initiation of inhaled corticosteroids, given
Unless a patient is mechanically ventilated, sedatives and instructions on medication use, given an action plan in case
narcotics have no role in the treatment of severe exacerbations symptoms worsen, and given specific instructions on medical
of asthma [1,2]. These agents depress the respiratory central follow-up [1,2,44,122].
drive to breathe that is critical for adequate minute ventilation. Patients who have an FEV1 or PEFR that is greater than
Theoretically, narcotics also may cause mast cell degranulation 40% but less than 70% after 4 hours of treatment have an in-
and worsen bronchospasm. complete response and require a careful triage decision. Some
patients do well if discharged with detailed instructions, close
medical follow-up, and continued systemic corticosteroids.
However, other patients do poorly if discharged. It has been
MANAGEMENT recommended that patients with incomplete responses be hos-
pitalized when there is any clinical feature to suggest high risk
Emergency Department for asthma mortality (Table 48.4). Patients with an FEV1 or
PEFR of less than 40% of predicted after 4 hours of intensive
The National Asthma Education and Prevention Program, con- bronchodilator therapy (poor response) should be hospitalized,
ducted under the auspices of the National Institutes of Health, often in an intensive care unit (ICU) setting.
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 48: Respiratory Failure Part III: Asthma 519

TA B L E 4 8 . 4 patients with less severe obstruction or those with intolera-


ble side effects, frequency can be reduced accordingly. Most
FACTORS FAVORING HOSPITALIZATION AFTER patients require 2 -adrenergic agonists a minimum of every
INITIAL BRONCHODILATOR THERAPY 4 hours; however, a recent study has shown that ad libitum
administration of albuterol every 4 hours is as effective as reg-
Poor response to initial therapy ularly timed administration of albuterol [133]. Evidence indi-
OR cates that delivery of 2 -adrenergic agonists by small-volume
Incomplete response to initial therapy and one or more of the nebulizer and delivery by MDI with spacer give equivalent re-
following: sults [1,2,72].
History of endotracheal intubation or ICU admission for Most hospitalized patients begin to show improvement in
asthma expiratory airflow after 6 to 12 hours of systemic corticosteroid
Recent emergency department visit for asthma therapy, but improvement sufficient for hospital discharge fre-
Recent hospitalization for asthma quently takes 2 to 7 days [134]. In one series, mean length
Multiple emergency department visits for asthma in last of hospital stay was 4 days, with a range of 0.5 to 17.0 days
year [135]. Expiratory airflow should be measured at least twice
Duration of current exacerbation >1 wk a day to assess the patients progress. Patient exercise toler-
Current use of oral corticosteroids ance and PEFR usually improve incrementally during hospi-
Home situation inadequate for follow-up talization, but it is common for patients recovering from ex-
Psychiatric conditions that may interfere with medical acerbations to have a hospital course punctuated by periods
compliance of worsening dyspnea, especially at night. These episodes of
History of syncope or seizures during prior exacerbations nocturnal worsening require patient assessment but generally
respond well to inhaled 2 -adrenergic agonists. When the ex-
piratory flow rate does not improve during the initial days of
hospitalization, additional or alternative diagnoses, especially
laryngeal dysfunction, congestive heart failure, and pulmonary
Treatment During Pregnancy thromboembolism, as well as gastroesophageal reflux disease
and sinusitis, should be considered.
Pregnancy should not alter treatment of an uncomplicated As the hospitalized patient recovers, the intensity of therapy
acute exacerbation of asthma. Because severe asthma exac- is decreased gradually. When the patient has minimal or no
erbations have been associated with increased perinatal mor- wheezing, is no longer awakened by dyspnea at night, can tol-
tality, probably due to maternal hypoxia and respiratory al- erate activity without oxygen desaturation of hemoglobin, and
kalosis [123,124], the excellent control of asthma should be has expiratory flow rates that have substantially improved, he
a main priority [125127] (see Chapter 51). However, un- or she is ready for hospital discharge. Patients generally should
fortunately, many pregnant women are suboptimally treated have a PEFR at least 70% of baseline at the time of discharge.
for asthma in the acute setting [128]. This is unfortunate be- Other patients with an incomplete response to therapy (50%
cause, in both the chronic and the acute setting, abundant ev- to 70% of baseline) should be assessed individually.
idence supports the safety of 2 -adrenergic agonist use dur- Discharge planning is important for preventing future ex-
ing pregnancy [125]. Also, although chronic administration acerbations (Table 48.5) [1,2,122]. Patients must be educated
of systemic corticosteroids throughout pregnancy appears to about asthma and the importance of seeking medical advice
carry some risk to the fetus [129], short courses of corticos- early in the course of exacerbations. Particularly important
teroids are considered safe for the fetus compared with the seri- are detailed instructions on MDI use, routine measurement of
ous risks associated with poorly controlled asthma. Therefore, PEFR, and keeping a symptom diary at home [136]. On dis-
corticosteroids should not be withheld from pregnant women charge, the patient is given medication instructions with partic-
who present with an acute asthma exacerbation. Treatment ular attention to oral and inhaled corticosteroids (see Corticos-
of chronic asthma during pregnancy should include inhaled teroids section) [61,105]. This is important, because bronchial
corticosteroids [130,131], which is important for preventing hyperresponsiveness remains high for at least 10 days after
development of acute asthma exacerbations [132]. discharge from an ICU for severe asthma [137]. Patients who
have recovered from an exacerbation of asthma should be in-
structed to use short-acting inhaled 2 -adrenergic agonists on
Routine Inpatient Management an as-needed basis only.

Most patients with severe exacerbations of asthma who are


admitted to the hospital can be monitored and managed safely
on a hospital ward that is well staffed by physicians, experi- TA B L E 4 8 . 5
enced nursing personnel, and respiratory therapists. However, DISCHARGE PLANNING
patients with severe airway obstruction who are at high risk
for mortality from asthma, especially those with an elevated Medications
PaCO2 (greater than 42 mm Hg) or changes in mental status Inhaled 2 -adrenergic agonists
despite initial intensive bronchodilator therapy, need the close Inhaled corticosteroids
monitoring of an ICU setting for possible intubation and me-
chanical ventilation. Oral corticosteroids (with plan for cessation)
Pharmacotherapy for hospitalized patients includes a con- Education
tinuation of the inhaled 2 -adrenergic agonists and systemic Avoidance of asthma triggers
corticosteroids begun in the emergency department [1,2]. Home monitoring of peak expiratory flow rates
Specifically, it is not recommended that ipratropium bromide Metered-dose inhaler techniques
be routinely continued once a patient is hospitalized [1]. For Action plan if relapse starts
patients with severe airway obstruction and only transient re- Appointment for medical follow-up
lief from treatment, inhaled 2 -adrenergic agonists can be ad- Asthma comanagement program
ministered frequently as needed (e.g., every 20 minutes). For
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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520 Section IV: Pulmonary Problems in the Intensive Care Unit

TA B L E 4 8 . 6
MANAGEMENT OF
RESPIRATORY FAILURE GOALS OF MECHANICAL VENTILATION

Maintain oxygen saturation of hemoglobin (>90%; 95%


Assessment during pregnancy)
Minimize dynamic hyperinflation
When severe hypoxemic or hypercapnic respiratory failure is
Decrease minute ventilation
present, mechanical ventilation is potentially life-saving. Even
Increase expiratory time
patients with severe obstruction can be supported with me-
Accept hypercarbia
chanical ventilation for the vital hours needed for corticos-
teroid action. However, mechanical ventilation for a severe Monitor closely for complications of mechanical ventilation
asthma exacerbation can be complicated by morbidity and
mortality, with mortality ranging from 0% to 38% in the lit-
erature [138140]. eter, 8 mm). A large endotracheal tube facilitates the option of
The decision to initiate mechanical ventilation for a se- therapeutic bronchoscopy at a later time.
vere asthma exacerbation should be based on a number of
considerations individualized for each patient [140]. For pa-
tients in severe distress in whom respiratory arrest has al-
ready occurred or is imminent, the need for intubation and
Invasive Mechanical Ventilation
mechanical ventilation is obvious. The possibility of pneumoth- The guiding principle for mechanical ventilation during a se-
orax should be promptly addressed in these patients. Patients vere exacerbation of asthma is to provide adequate oxygena-
who are not in extremis should be monitored closely during tion while minimizing the risk of barotrauma (Table 48.6).
initial bronchodilator therapy, and the physician should be Because the risk of barotrauma is related to dynamic
prepared to perform intubation in case of substantial dete- hyperinflation of the lungs and high plateau airway pressures,
rioration. The decision to intubate during a severe asthma a ventilatory strategy that minimizes lung volumes and airway
exacerbation is a clinical judgment. In severely obstructed pressures should be used [1,2,6,7,140]. (See Chapter 58 for a
patients with decreasing objective measures of airflow, worsen- discussion of initiating mechanical ventilation.)
ing mental status, or signs of respiratory muscle fatigue despite With outmoded mechanical ventilation strategies that aimed
bronchodilator therapy, urgent intubation and mechanical ven- to normalize the PaCO2 , high tidal volumes and rapid frequen-
tilation should be strongly considered. In general, any patient cies of ventilation were required, and this promoted increased
who responds poorly to initial bronchodilator therapy and has air trapping and high airway pressures. Most authorities now
an initial PaCO2 of 40 mm Hg or more in association with believe that high airway pressures are to be avoided because
moderately severe hypoxemia should have close serial ABG they are a major cause of serious morbidity and mortality
monitoring. In patients with a PaCO2 of greater than 55 to during mechanical ventilation of asthmatic patients [140,145
70 mm Hg, increasing PaCO2 (greater than 5 mm Hg per hour) 147].
in association with a PaO2 of less than 60 mm Hg or the pres- The modern strategy for mechanical ventilation for a se-
ence of metabolic acidosis, intubation and mechanical ventila- vere exacerbation of asthma is controlled hypoventilation with
tion should be very strongly considered [52,138]. However, it is permissive hypercapnia [6,7,140,145148] (see Chapter 58).
emphasized that when clinical signs indicate a need for intuba- This strategy does not attempt to establish a normal PaCO2 as
tion, the decision to intubate should be made immediately and long as the minute ventilation and fraction of inspired oxygen
never delayed, waiting for an ABG result. The role of nonin- maintain adequate tissue oxygenation. Physician acceptance
vasive positive-pressure ventilation in managing patients with of hypercapnia in this setting is termed permissive hypercap-
acute asthma is not established and NIH asthma guidelines do nia [145147]. When possible, measurement of volume at end
not make recommendations on its application, considering it inspiration should be part of the management plan to moni-
experimental at this time [1,141143] (see Chapter 59). tor for the development of dynamic hyperinflation [149] (see
Chapter 58).
Although the use of sodium bicarbonate to treat acidosis
Endotracheal Intubation is controversial, advocates for its use in severe acute respira-
tory acidosis have regarded a pH of 7.20 to be the minimum
Airway control should be established by the most experienced safe level [150]. This impression and the practice of infusing
personnel available because even minor manipulation of the sodium bicarbonate to maintain a pH of more than 7.2 is based
larynx and trachea can precipitate vagal reflexes that elicit on two uncontrolled studies in which stuporous and comatose
laryngospasm and bronchospasm [140]. Atropine can be given patients with acute respiratory acidosis markedly and quickly
before intubation to attenuate these vagally mediated reflexes. improved when infusion of sodium bicarbonate increased the
Lidocaine can be used to achieve topical anesthesia of the pH to greater than 7.2 [151,152]. However, no controlled stud-
hypopharynx and larynx, but even lidocaine has been asso- ies of respiratory acidosis support the use of sodium bicarbon-
ciated with bronchospasm [144]. Administration of a short- ate to maintain a specific pH value.
and rapid-acting intravenous benzodiazepine often can facili- The physiologic responses to metabolic and respiratory aci-
tate patient relaxation and preoxygenation, allowing time for dosis include increases in cardiac output, pulmonary arterial
a controlled intubation that minimally irritates the larynx and pressure, and heart rate, whereas systemic vascular resistance
trachea. Opiates are not used for intubation or sedation in decreases and mean systemic arterial pressure remains un-
asthmatic patients because narcotics can provoke nausea and changed [153155]. In diseased lungs, PaO2 improves [153].
vomiting and theoretically can provoke histamine release that The hemodynamic changes are mediated directly by endoge-
worsens bronchospasm. nous secretion of catecholamines, primarily norepinephrine,
Oral, rather than nasal, intubation is preferred in patients stimulated by decreases in pH. The effects of sodium bicar-
with a severe asthma exacerbation because nasal polyps and bonate infusions on these hemodynamic responses and gas
sinusitis are common in asthma and because the oral route exchange have been studied. As the acidosis lessens, car-
allows placement of a larger endotracheal tube (internal diam- diac output and PaO2 worsen [154,155]. Moreover, sodium
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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Chapter 48: Respiratory Failure Part III: Asthma 521

bicarbonate infusions have been shown neither to improve sur- Barotrauma is a major cause of morbidity and mortality
vival nor to enhance bronchodilation. Although studies from among patients receiving mechanical ventilation for severe ex-
the 1950s and 1960s suggested that endogenous epinephrine acerbations of asthma [140,148,164]. High plateau airway
release was depressed in acidosis, more recent studies have con- pressures are associated with overdistended alveoli that rup-
clusively shown that it is either unchanged or augmented [155]. ture. Air may dissect along the bronchovascular interstitium
Because carbon dioxide is generated when infused sodium bi- and sometimes is evident on chest radiograph as parenchy-
carbonate buffers hydrogen ions, infusion of sodium bicarbon- mal air cysts, linear air streaks emanating from the hila, and
ate predictably raises carbon dioxide tensions in blood [156]. perivascular air halos [165,166]. As the air dissects centrally,
Because carbon dioxide readily diffuses across cell membranes, mediastinal and subcutaneous emphysema develop. As an al-
sodium bicarbonate therapy may cause paradoxic intracellular ternative, air from ruptured alveoli may dissect through the
acidosis [157], and this may adversely affect survival. For these pleural surfaces into the pleural space to create a pneumotho-
reasons, we suggest use of sodium bicarbonate only when the rax [167]. For patients on mechanical ventilation, pneumoth-
acidosis appears to be adversely affecting the patients hemo- orax progresses to tension pneumothorax rapidly and always
dynamic status. should be treated immediately with tube thoracostomy. It must
In managing patients during mechanical controlled hy- be presumed, emergently, that any pneumothorax during me-
poventilation with permissive hypercapnia, the minimum safe chanical ventilation is under tension [168]. (See Chapter 58
pH is not known. In three uncontrolled studies, pH values for the discussion of minimizing barotrauma during mechani-
were not maintained at greater than 7.2, and outcomes did cal ventilation.)
not appear to be adversely affected. Sodium bicarbonate was Mucous plugging commonly occurs during acute exacerba-
not given in one study unless pH was less than 7.15 [149]; in tions of asthma. Large mucous plugs occluding the endotra-
the other two studies, it was not given to any patient even when cheal tube should be considered when there is insurmountable
pH was 7.02 and less than 7.00 [145,158]. difficulty in ventilating a patient. Large mucous plugs also may
Neuromuscular blocking agents, such as pancuronium, ve- cause lobar or lung atelectasis that impairs gas exchange and
curonium, and atracurium, can be used to help maintain low increases airway pressures. Therapeutic bronchoscopy may be
airway pressures during delivery of mechanical ventilation (see considered to relieve large mucous plugs if conservative mea-
Chapter 25). Paralyzing skeletal muscles prevents the devel- sures, corticosteroids, and bronchodilators are not effective.
opment of high airway pressures due to the patient bucking Retained secretions and atelectasis also contribute to the sig-
or fighting the ventilator. Notably, a side effect of neuromus- nificant risk of nosocomial pneumonia during mechanical ven-
cular blocking agents can be severe bronchospasm. Vecuro- tilation [169].
nium is often reported to be unlikely to cause bronchospasm, Other complications are indirectly related to mechanical
but case reports suggest that vecuronium too can rarely cause ventilation. Thromboembolism and gastric stress ulcers may
bronchospasm [159]. Another adverse effect of these agents occur with greater frequency in patients with severe exacerba-
is that patients who undergo even brief neuromuscular block- tions of asthma [170]. Arrhythmias and hypokalemia may oc-
ade in conjunction with corticosteroid administration have a cur during treatment for acute asthma because of therapy with
risk of developing a prolonged and sometimes severe myopathy sympathomimetic drugs. Hypophosphatemia may develop sec-
[160]. Because all patients with severe exacerbations of asthma ondary to alkalosis [171].
are treated with corticosteroids, paralyzing agents should be
avoided whenever possible. For patients who cannot be man-
aged without neuromuscular blockade, continuous infusions
of neuromuscular blocking agents should be avoided and mus-
Additional and Unconventional
cle function should be allowed to recover partially between Management Measures
repetitive boluses.
Mechanical ventilation accomplishes the work of breathing Even after using bronchodilators, corticosteroids, sodium bi-
while the severely obstructed patient is treated intensively with carbonate, and mechanical ventilation, airway obstruction
inhaled bronchodilators and glucocorticoids. With this inten- sometimes is sufficiently severe to prevent maintenance of an
sive pharmacologic therapy, mechanical ventilation usually can acceptable arterial pH or adequate tissue oxygenation. In these
be discontinued in 1 to 3 days once discontinuation guidelines rare cases, additional, sometimes unconventional, measures
are met [140,161163] (see Chapter 60). Some patients may can be used to support the patient until corticosteroids have had
require 2 to 4 weeks of mechanical ventilation, especially when time to suppress the underlying inflammatory process. Some of
pneumonia complicates an acute exacerbation of asthma. these measures are based on anecdotal experience (Table 48.7).
If airway pressures remain high on mechanical ventilation
despite the proper application of controlled hypoventilation
Complications of Mechanical Ventilation with permissive hypercapnia, delivering heliox by mechanical
ventilation has been suggested to allow adequate ventilation
Serious complications have been reported as a result of
mechanical ventilation for severe exacerbations of asthma
[138,139,140,148]. Most of these are preventable or treatable TA B L E 4 8 . 7
if detected early. Problems with airway control, including trau-
matic and esophageal intubation, should always be anticipated. SPECIAL OR UNCONVENTIONAL THERAPEUTIC
Intubation of the right mainstem bronchus is a serious problem MEASURES
of airway control because delivery of tidal volumes to one lung
increases the risk of barotrauma. Once an airway is established Intravenous 2 -adrenergic agonists
and mechanical ventilation initiated, hypotension may occur Methylxanthines
because high intrathoracic pressures that occur during mechan- Heliumoxygen mixtures delivered through the ventilator
ical ventilation in severe asthma exacerbations impede venous General anesthetics
return to the right ventricle of the heart. This is treated by Bronchoscopy with therapeutic lavage (intubated patients only)
administering intravenous fluids and adjusting tidal volumes, Hypothermia
respiratory frequency, and inspiratory flow to decrease hyper- Extracorporeal life support
inflation and intrinsic positive end-expiratory pressure [164].
P1: OSO/OVY P2: OSO/OVY QC: OSO/OVY T1: OSO Printer: Prepress
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522 Section IV: Pulmonary Problems in the Intensive Care Unit

of the patient at reduced airway pressures [172]. Caution is TA B L E 4 8 . 8


necessary when using heliox in this setting because the low
density of the gas mixture makes ventilator settings inaccurate TREATMENT OF ACUTE ASTHMA: RANDOMIZED
(e.g., tidal volume) [173]. CONTROLLED TRIALS AND META-ANALYSES
Bronchospasm usually is not the major factor limiting air-
flow in patients who are already being maximally treated for an -Adrenergic agonists are first-line therapy for acute
acute exacerbation of asthma. However, for those who fail to asthma because they are rapidly acting and provide more
respond to maximal conventional therapy, a variety of strate- bronchodilation than methylxanthines and cholinergic
gies have been advocated to maximize bronchodilation. Some antagonists [62].
reports suggest that intravenous 2 -adrenergic agonists may Metered-dose inhalers with a holding chamber are at least
significantly improve airway obstruction in select patients but as effective as wet nebulization for the delivery of
this treatment is not established and not recommended in cur- -adrenergic agonists in the treatment of acute asthma
rent NIH asthma guidelines because of danger of cardiac toxic- [72,73].
ity [1,83,84]. General anesthetics are excellent bronchodilators Adding inhaled ipratropium bromide to treatment with
and an important option for patients whose conditions are re- -adrenergic agonists provides benefit to adults with acute
fractory to maximal routine therapy. Anecdotally, halothane asthma in the emergency department [88].
[174,175], thiopental [176], ketamine [177,178], and isoflu- In hospitalized adult patients with acute asthma, systemic
rane [179] all have been used successfully to treat patients with glucocorticoids speed improvement of symptoms and lung
severe asthma exacerbations. If general anesthetics are used, an function [96].
anesthesiologist should be consulted. In addition to a short course of oral corticosteroids, initiate
Because a major cause of airway obstruction during an acute or continue daily inhaled corticosteroids on emergency
exacerbation of asthma is mucous plugging, therapeutic bron- room discharge of patients with persistent asthma [186].
choscopy with lavage has been used as an additional supportive
measure in patients who are extremely difficult to ventilate ade-
quately [180182]. While therapeutic bronchoscopy is not per- administered through a bronchoscope to relieve mucous plug-
formed routinely in asthma because worsening bronchospasm ging causing atelectasis in a child with asthma [183].
is a recognized complication of bronchoscopy in asthmatics, Case reports describe unconventional measures that might
should the need arise, a flexible bronchoscope with a large be considered for the management of rare, exceedingly diffi-
suction channel should be used, and the mechanically venti- cult cases. For example, hypothermia and extracorporeal life
lated patient should be sedated. N-acetylcysteine, a mucolytic support have been methods used to support critically ill pa-
agent, is associated with bronchospasm in asthmatic patients tients whose conditions are refractory to conventional therapy
but, anecdotally, has been used successfully during therapeutic [184,185].
bronchoscopy by delivering a dilute solution (less than 1%) Advances in asthma, based on randomized, controlled trials
through the bronchoscope to dissolve mucous plugs [180]. or meta-analyses of such trials, are summarized in Table 48.8
DNase (2.5 mg in 10 mL of sterile normal saline) has been [186].

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CHAPTER 49 RESPIRATORY FAILURE


PART IV: CHRONIC OBSTRUCTIVE
PULMONARY DISEASE
MEYER S. BALTER AND RONALD F. GROSSMAN

Chronic obstructive pulmonary disease (COPD) is defined in


the National Heart, Lung, and Blood Institute/World Health ETIOLOGY
Organization Global Initiative for Chronic Obstructive Lung
Disease as a disease state characterized by airflow limitation The major risk factor associated with the development of
that is not fully reversible [1]. The airflow limitation is usually COPD is cigarette smoking [6]. The total number of pack-
both progressive and associated with an abnormal inflamma- years of smoking correlates best with development of COPD
tory response of the lungs to noxious particles or gases. Any [7,8], although the total length of time spent smoking proba-
patient presenting with symptoms of cough, sputum produc- bly contributes as well [8]. Significant COPD develops in only
tion, or dyspnea, and/or a history of exposure to risk factors a minority of even heavy cigarette smokers [9], suggesting that
should be considered as having the diagnosis of COPD. The di- some cofactor(s) (e.g., host susceptibility) must be important.
agnosis can be confirmed by spirometry especially if the forced Homozygous 1 -antitrypsin deficiency (a relatively rare condi-
expired volume of air in 1 second (FEV1 ) measured after in- tion) is a risk factor for the development of COPD [10] even
haled bronchodilator (postbronchodilator FEV1 ) is less than in the absence of cigarette smoking. It has been estimated that
80% of the predicted value in combination with an FEV1 to approximately 60,000 patients in the United States have this
forced vital capacity ratio less than 70%. condition but only a minority are treated [10]. COPD does not
Although a variety of conditions characterized by chronic necessarily develop in nonsmoking patients with 1 -antitrypsin
airflow obstruction have been termed COPD, the presence deficiency, which may explain why only a minority of patients
of largely irreversible chronic airflow obstruction predomi- with this condition are treated. Various other factors may in-
nantly in current or former cigarette smokers is the meaning crease the risk of COPD, including childhood respiratory ill-
commonly used in the subsequent discussion. Emphysema is nesses, adenovirus infection, air pollution, the presence of in-
the underlying disease process that is mainly responsible for creased airway reactivity, and occupational exposures [11].
severe airflow obstruction. The distinction between chronic
obstructive bronchitis, bronchiolitis, and emphysema is diffi-
cult to make with precision and is usually clinically unimpor-
tant.
PATHOPHYSIOLOGY
COPD affects more than 5% of the adult population and
is associated with increasing morbidity and mortality in the Pathogenesis
United States and other countries [2]. Mortality rates in the
United States have increased from 25.6 per 100,000 population Respiratory bronchiolitis is the initial lesion seen in smok-
in 1979 to 40.5 per 100,000 population in 2006 [3]. Approxi- ers [12]. The inflammatory process may progress in suscep-
mately 750,000 admissions to hospital annually in the United tible people to glandular enlargement in bronchi, goblet cell
States can be directly attributed to COPD, and the costs asso- metaplasia, smooth muscle hypertrophy, inflammation in mem-
ciated with the care of all COPD patients has been estimated to branous bronchioles, worsening respiratory bronchiolitis, and
be around $24 billion [4]. The World Health Organization has parenchymal involvement with emphysema [13]. The progres-
predicted that COPD will be the third leading cause of death sion of COPD is strongly associated with an increase in the vol-
and fifth leading cause of disability worldwide by 2020 [5]. ume of tissue in the wall and the accumulation of inflammatory
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526 Section IV: Pulmonary Problems in the Intensive Care Unit

mucous exudates in the lumen of small airways [14]. Nor- have shown a consistent association between chronic mucus
mally, a relative balance exists between destructive proteolytic hypersecretion and both an accelerated decline in FEV1 and an
enzymes, which are released in the lung as a result of inflamma- increased risk of subsequent hospitalization [23]. A history of
tion, and various inhibitory, antiproteolytic substances, which dyspnea on exertion in a heavy cigarette smoker should always
act to dampen the response and limit the damage [15]. In some raise the possibility of COPD, which can then be confirmed by
cigarette smokers, there may be a genetic tendency favoring a objective investigations.
greater inflammatory and destructive response to certain ele- The physical examination can distinguish patients who
ments of cigarette smoke. Population studies show a definite should undergo objective laboratory testing, but it is less ac-
familial tendency toward COPD [16], and pulmonary function curate than PFTs in detecting and quantifying the severity of
comparison studies of identical twins suggest a genetic suscep- COPD [24]. The most useful physical finding is a definite de-
tibility [17]. crease in breath sound intensity [25,26]. Other suggestive clin-
COPD is characterized by chronic inflammation through- ical signs include hyperinflation, prolonged forced expiratory
out the airways, parenchyma, and pulmonary vasculature. time, and wheezing.
Macrophages, T lymphocytes (predominately CD8+), and A combative, confused, or obtunded patient should alert the
neutrophils are increased in various parts of the lung [18]. physician to the possibility of hypercapnia or hypoxia. Respira-
Activated inflammatory cells release a variety of mediators tory muscle fatigue is heralded by new onset of paradoxical res-
including leukotriene B4, interleukin-8, tumor necrosis factor- piratory motion or respiratory alternans [27]. During normal
, and otherscapable of damaging lung structures and/or sus- inspiration, the rib cage moves upward and outward, and the
taining neutrophilic inflammation [5]. There is a relationship anterior abdominal wall moves outward. With diaphragmatic
between the extent of airway occlusion by inflammatory mucus fatigue, the anterior abdominal wall may move inward during
exudates and the severity of COPD [14]. inspiration and outward during expiration. Respiratory alter-
nans describes alternate abdominal (diaphragmatic) breathing
and rib cage (intercostal) breathing. When overt, this condi-
Physiologic Derangements tion can be detected clinically by observing dramatic shifts
in relative movement of the abdomen and rib cage every few
Expiratory airflow obstruction results from structural airway breaths.
narrowing as well as functional narrowing due to loss of ra-
dial distending forces on the airways. Inflammatory edema, ex-
cessive mucus, and glandular hypertrophy are responsible for Radiology
intrinsic obstruction of airways. Destruction of alveolar walls
causes loss of elastic recoil and airflow obstruction, which in- Radiographic findings may include (a) hyperinflation with flat-
creases in a dynamic fashion with expiratory effort. tened diaphragmatic domes and increased retrosternal and
The pathophysiologic consequences of severe, chronic air- retrocardiac air space; (b) one of two distinctly different bron-
flow obstruction in the lung include (a) reduced flow rates chovascular patterns, vascular attenuation or prominence of
that limit minute ventilation; (b) maldistributed ventilation, re- lung markings; (c) enlarged hilar pulmonary arteries and right
Q]
sulting in wasted ventilation (high ventilation-perfusion [V/ ventricular enlargement; and (d) regional hyperlucency and

mismatch) and impaired gas exchange (low V/Q mismatch) bullae [28]. Radiographic studies have low sensitivity for the
[19]; (c) increased airway resistance, which causes increased diagnosis of mild COPD [29].
work of breathing [19]; and (d) air trapping and hyperinfla- Computed tomography scanning of the chest is superior to
tion, which alter the geometry of the respiratory muscles and the chest radiograph in diagnosing emphysema and determin-
place them at a mechanical disadvantage. The maximum force ing the nature and the extent of the disease [29]. Centrilobular
that they are capable of generating is decreased, which may emphysema is characterized by the upper lobe distribution of
predispose them to fatigue [20]. In addition to these factors, focal areas of low attenuation usually less than 1 cm in di-
some patients with COPD may have a blunted respiratory cen- ameter. Panlobular emphysema is frequently more recognized
ter drive, which further predisposes them to carbon dioxide in the lower lobes and there is a generalized decrease in lung
retention [21]. markings with few blood vessels.
In patients presenting with acute deterioration in respiratory
status, a chest radiograph may exclude reversible conditions
such as pneumonia, pleural effusion, pneumothorax, atelec-
DIAGNOSIS tasis, and pulmonary edema. However, the diagnostic yield of
routine radiographs is low [30]. In the intensive care unit (ICU),
The diagnosis of COPD is based on clinical grounds but con- technical factors limit the quality of the chest films, making in-
firmed by pulmonary function tests (PFTs). Arterial blood gas terpretation of a portable anteroposterior film even more diffi-
(ABG) values determine the diagnosis of respiratory failure. cult. Nevertheless, these studies provide valuable information,
Clinical findings are used primarily to suggest the diagno- particularly in patients receiving mechanical ventilation.
sis, which then must be confirmed on the basis of laboratory
findings.
Pulmonary Function Tests
History and Physical Examination A decrease in the ratio of FEV1 to forced vital capacity is the
hallmark of obstructive airways disease and is useful in the
A chronic productive cough and dyspnea on exertion are the diagnosis of mild disease. However, it is the FEV1 that is cor-
two symptoms most commonly associated with COPD. How- related with clinical outcome and mortality [23]. Hypercap-
ever, a history of a chronic productive cough is nonspecific and nic respiratory failure from COPD is extremely unlikely unless
may result from a variety of other conditions. Previous stud- FEV1 is less than 1.3 L [31] and is usually not observed unless
ies indicated that there was little correlation found between a FEV1 is less than 1 L. COPD is also associated with an increase
chronic productive cough (reflecting large-airway mucus hy- in total lung capacity and residual volume and a reduction in
persecretion) and the development of significant airflow limi- carbon monoxide diffusing capacity [32].
tation (predominantly a manifestation of disease of small air- PFTs are essential for the diagnosis and estimating the sever-
ways less than 2 mm in diameter) [22]. However, recent studies ity of COPD; on the other hand, ABG values provide the data
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Chapter 49: Respiratory Failure Part IV: Chronic Obstructive Pulmonary Disease 527

necessary to diagnose and quantitate the severity of respira- TA B L E 4 9 . 1


tory failure. The patient with severe COPD typically presents
with an elevated arterial carbon dioxide tension (PaCO2 ), sub- DIFFERENTIAL DIAGNOSIS OF ACUTE
stantially decreased arterial oxygen tension (PaO2 ), and an DECOMPENSATION IN CHRONIC OBSTRUCTIVE
alveolararterial oxygen tension gradient that is significantly PULMONARY DISEASE
increased [33].
Air pollution
Aspiration
Bronchiolitis
DIFFERENTIAL DIAGNOSIS Carcinoid syndrome
Cardiac arrhythmia
Asthma, cystic fibrosis, bronchiectasis, and bronchiolitis oblit- Chest wall injury (e.g., rib fracture)
erans all can cause expiratory airflow obstruction. A previ- Cigarette smoking
ous PFT demonstrating reversibility of the airflow obstruction, Cystic fibrosis
younger age, presence of blood or sputum eosinophilia, ab- Lymphangitic carcinomatosis
sence of cigarette smoking, and presence of expiratory and in- Metabolic derangements (e.g., hypophosphatemia)
spiratory monophonic wheezing are all suggestive of asthma. Parasitic infections
Cystic fibrosis is diagnosed on the basis of a positive sweat Pleural effusion
chloride test in a patient with obstructive lung disease, positive Pneumonia
family history for cystic fibrosis, or pancreatic insufficiency. Pneumothorax
Bronchiectasis may be suggested by a history of copious spu- Pulmonary edema
tum production, by recurrent chest infections or hemoptysis, Pulmonary embolism
or from the chest radiograph. Sedation
Surgery
Systemic illness
Tracheobronchial infection
FACTORS CAUSING AN Upper respiratory tract infection
EXACERBATION OF CHRONIC
OBSTRUCTIVE PULMONARY
DISEASE
Chronic Management
According to WHO/NHLBI Global Initiative for Chronic Ob-
structive Lung Disease (GOLD) document an acute exacerba- Once COPD is diagnosed, smoking cessation is the most im-
tion is defined as an event in the natural course of the disease portant and obvious first step in management. The annual de-
characterized by a change in the patients baseline dyspnea, cline in FEV1 has been demonstrated to be less in ex-smokers
cough, and/or sputum that is beyond normal day-to-day vari- than in current smokers [6]. The success of smoking cessa-
ations, is acute in onset, and may warrant a change in regular tion programs is limited, with a 70% to 80% relapse rate in
medications in a patient with underlying COPD [34]. This the first year. However, nicotine replacement therapy, the an-
can be accompanied by a change in the color and consistency tidepressant bupropion, and repeated counseling are effective
of the expectorated sputum, a feature that is predictive of bac- in increasing quit rates [39]. The addition of varenicline, an
terial infection [35]. Expiratory airflow obstruction is wors- 4 2 nicotinic receptor partial agonist, has improved cigarette-
ened, the work of breathing increases, and mucus production smoking quit rates [40]. Annual influenza vaccination is a
or mucociliary clearance, or both, are altered. Although many useful, cost-effective preventive measure and has been shown
factors may be associated with an acute exacerbation (Table to decrease morbidity and mortality related to influenza even
49.1), the most commonly identified cause is an acute upper or among patients with chronic respiratory disease [41,42]. Data
lower respiratory tract infection that may be viral or bacterial regarding the benefit of pneumococcal vaccination are limited
in etiology [36]. Spirometry shows worsened expiratory airflow to bacteremic pneumococcal infection, but a decrease in hospi-
obstruction, whereas ABGs usually demonstrate an additional talizations and deaths among vaccinated patients with COPD
decrease in the PaO2 and, in patients with severe COPD, devel- has been observed in observational studies [43].
opment or worsening of arterial hypercapnia. Systemic effects Inhaled bronchodilators improve airflow obstruction, al-
such as fever and neutrophilia are uncommon, and the chest though to a less marked degree than in asthmatic patients,
radiograph typically shows no new abnormality. and improve exercise capacity and quality of life [44]. Al-
Some of the other factors listed in Table 49.1 may be eas- though -agonists and the anticholinergic agent ipratropium
ily recognizable, such as a large pneumothorax or pneumonia, bromide are efficacious, the combination is more effective
but others may be subtle, such as an electrolyte abnormality than either of the two agents alone [45]. Long-acting 2 -
or unrecognized use of drugs that can cause respiratory cen- adrenergic agonists in combination with ipratropium or theo-
ter depression. Furthermore, events such as pulmonary em- phylline are superior to either agent alone, and a long-acting 2 -
bolism may go totally unrecognized because clinical findings adrenergic agonist combined with ipratropium is more effective
such as dyspnea or tachypnea may be attributed to the under- than the short-acting 2 -adrenergic agonist plus ipratropium
lying COPD itself [37] and may be more common than previ- [46,47]. A long-acting 2 -adrenergic agonist appears to offer
ously thought [38]. the additional benefit of extending the time to an exacerbation
[47]. Long-acting anticholinergics have been demonstrated to
improve lung function, reduce exacerbations, and improve
health-related quality of life [48,49]. In addition to some bron-
TREATMENT chodilator effects, theophylline may have beneficial effects on
diaphragmatic strength, resistance to fatigue, and central ner-
Treatment of the patient with COPD involves chronic manage- vous system (CNS) respiratory drive [50,51]. This agent pro-
ment of the stable patient, treatment of acute exacerbations duces a clinical benefit in some patients with COPD [52] but,
(Table 49.1), and treatment of respiratory failure. with its narrow therapeutic window, the potential for toxicity
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528 Section IV: Pulmonary Problems in the Intensive Care Unit

must be recognized. All categories of bronchodilators have sistance in COPD patients have not been uniformly reported,
been shown to increase exercise capacity in COPD without nec- but there may be a role for selected patients [72].
essarily producing significant changes in FEV1 probably by de-
creasing dynamic hyperinflation. Regular treatment with long-
acting bronchodilators is more effective and convenient than Acute Exacerbation
treatment with short-acting bronchodilators, but more expen-
sive. They safely attenuate airflow obstruction, decrease the Treatment of acute exacerbation can be divided into two pri-
frequency and severity of symptoms by reducing the amount mary methods: supportive and specific.
of dynamic hyperinflation, and improve quality of life [53].
Although oral corticosteroids are not routinely recom- Supportive Therapy
mended in the chronic management of patients with COPD, a
small subgroup of patients does benefit [54]. A corticosteroid Oxygen Therapy. Supplemental oxygen therapy should be ad-
trial, with PFTs before and after a 2-week course of 20 to 40 ministered to all hypoxemic patients who present with an acute
mg prednisone daily, has been recommended in the past to exacerbation. The PaCO2 commonly rises somewhat when a
identify these patients. More recent studies suggest, however, patient with COPD receives supplemental oxygen, but carbon
that this is a poor predictor of long-term response to inhaled dioxide narcosis due to oxygen therapy is uncommon [73]. Pa-
corticosteroids [55]. Several studies have documented little ef- tients should not be kept hypoxemic for fear that oxygen ther-
fect on the rate of lung function decline with inhaled corticos- apy will aggravate carbon dioxide retention, but ABG values
teroid therapy, but the severity and number of exacerbations should be closely monitored. Supplemental oxygen therapy is
may be reduced, especially among patients with frequent ex- discussed later in this chapter (see Respiratory Failure section)
acerbations [56,57]. Short-term treatment with a combined in- and in Chapter 62.
haled glucocorticosteroid and long-acting -agonist resulted in
greater control of lung function and symptoms than combined Bronchodilators. Although COPD is characterized by poorly
anticholinergic and short-acting -agonist [58]. Analysis of a reversible airflow obstruction, there is frequently a significant
number of placebo-controlled trials of inhaled corticosteroids reversible component, particularly in the setting of an acute ex-
has demonstrated a reduction in all-cause mortality by about acerbation. Many patients with acute exacerbations of COPD
25% relative to placebo [59]. Stratification by individual tri- respond to these agents with some improvement in airflow ob-
als and adjustments for age, sex, baseline postbronchodilator struction [74]. Inhaled -agonists and ipratropium appear to be
percentage predicted FEV1 , smoking status, and body mass in- equally effective bronchodilators in patients with acute exac-
dex do not materially change the results. Former smokers and erbations [75]. These agents can be administered by nebulizer
women seem to benefit the most. or, with equal efficacy, by metered-dose inhaler using a spacer
There is a growing body of evidence to suggest that the use device [76]. A metered-dose inhaler with an aerosol holding
of a combination of inhaled corticosteroids and long-acting 2 - chamber also can be used effectively for patients on mechani-
agonists improves lung function, symptoms, and health status cal ventilation and is as effective as a nebulizer [77]. For specific
and reduces exacerbations in patients with moderate-to-severe details on the use of these agents, see Chapter 62.
COPD [60]. There may also be a survival benefit. A subsequent The role of theophylline in acute exacerbations is less
post hoc analysis of the Toward a Revolution in COPD Health well accepted than in chronic management. A double-blind,
(TORCH) study indicated that pharmacotherapy with salme- placebo-controlled trial demonstrated no additional benefit of
terol plus fluticasone propionate, or the components, reduced aminophylline over standard therapy, but increased adverse ef-
the rate of decline of FEV1 in patients with moderate-to-severe fects were noted [78].
COPD, thus slowing disease progression [61].
The addition of a combination of inhaled corticosteroid Antibiotics. Although there is no evidence that antibiotics
and long-acting 2 -agonist (salmeterol plus fluticasone) to a given routinely are beneficial in all exacerbations of COPD, an-
long-acting anticholinergic (tiotropium) improved lung func- tibiotic therapy is appropriate, particularly in more severe ex-
tion, health status and reduced hospitalizations compared with acerbations (i.e., patients experiencing increased dyspnea and
the use of a long-acting anticholinergics alone [62]. Therapy cough with increased sputum volume or purulence) [79]. Fre-
with tiotropium added to other respiratory medication (mainly quently, bacteria can be isolated from lower airway samples of
a combination of inhaled corticosteroid and long-acting 2 - patients who have COPD in the stable state. This is known as
agonist) was associated with improvements in lung function, lower airway bacterial colonization and the presence of these
quality of life, and exacerbations during a 4-year period but organisms is associated with increased frequency and severity
did not significantly reduce the rate of decline in FEV1 [63]. of exacerbations and a more rapid decline in FEV1 [80]. Micro-
Long-term oxygen therapy used for at least 15 hours per biologic surveys in patients with severe exacerbations requiring
day in patients with severe COPD and hypoxia when breathing mechanical ventilation reveal that potentially pathogenic or-
room air is associated with prolonged survival and improved ganisms can be found in 72% [81]. The rate of Gram-negative
quality of life, increasing life span by 6 to 7 years [64,65]. enteric bacilli and Pseudomonas was high (30%) and could
Oxygen therapy is recommended for patients with a PaO2 of not be predicted clinically. Although the results of a number of
less than 55 mm Hg and those with a PaO2 of 55 to 59 mm Hg earlier, poorly designed studies are inconclusive (Table 49.2), a
who have polycythemia or right-sided heart failure. Significant double-blind, placebo-controlled study on the effects of broad-
increases in PaCO2 usually do not occur as a result of this spectrum antibiotics on exacerbations of COPD demonstrated
therapy [66]. significant benefit [35]. Antibiotic treatment produced signif-
Pulmonary rehabilitation programs have been demon- icantly earlier resolution of symptoms and prevented clinical
strated to improve exercise tolerance and reduce dyspnea and deterioration [35]. A meta-analysis confirmed these observa-
should be part of routine management for patients with sig- tions, suggesting that antibiotics are useful, particularly in pa-
nificant COPD [6769]. Nocturnal negative-pressure ventila- tients with significant impairment of lung function [82]. An-
tory assistance has been used to rest respiratory muscles [70]. other meta-analysis suggested antibiotics reduced the risk of
Whether this intervention is beneficial is unclear, as a large short-term mortality by 77%, decreased the risk of treatment
controlled trial failed to demonstrate improvement in exercise failure by 53% and the risk of sputum purulence by 44%; with
tolerance, ABG values, or quality of life [71]. Successful thera- a small increase in the risk of diarrhea [83]. Clinical benefits
peutic results with nocturnal noninvasive positive-pressure as- from antibiotic therapy are most likely to occur in patients
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Chapter 49: Respiratory Failure Part IV: Chronic Obstructive Pulmonary Disease 529

TA B L E 4 9 . 2
SUMMARY OF PLACEBO-CONTROLLED TRIALS OF ANTIBIOTIC USE IN EXACERBATIONS OF CHRONIC
OBSTRUCTIVE PULMONARY DISEASE

No. of
patients Antibiotic Regimen Outcome Reference

71 TMP-SMX or amoxicillin 14-d course No accelerated recovery [132]


173 TMP-SMX, amoxicillin, or Ambulatory, 10-d course Earlier resolution of symptoms; [35]
doxycycline prevented deterioration
40 Tetracycline Hospitalized, 7-d course No benefit over placebo [133]
259 Tetracycline or chloramphenicol Ambulatory, 12-d course Earlier recovery; no difference at [134]
1 mo
30 Penicillin + streptomycin Hospitalized, parenteral therapy Prevented deterioration [135]
56 Ampicillin Hospitalized, 7-d course No benefit over placebo [136]

TMP-SMX, trimethoprim-sulfamethoxazole.

with more serious exacerbations, particularly those with fever evidence to suggest that these modalities are effective in the
and grossly purulent sputum [84]. The organisms that are usu- COPD patient in exacerbation in the absence of bronchiecta-
ally responsible for bacterial infection in acute exacerbations sis or bronchorrhea, or both (expectoration of sputum greater
include Haemophilus influenzae, Streptococcus pneumoniae, than 30 mL per 24 hours).
and Moraxella catarrhalis. Between 20% and 40% of strains Patients with severe COPD are frequently nutrition-
of H. influenzae and 80% to 90% of strains of M. catarrhalis ally depleted, contributing to their overall poor status and
are -lactamase-producing and are resistant to -lactam an- decreased respiratory muscle strength [92,93]. Nutritional
tibiotics such as amoxicillin, although the rate of resistance of support should be instituted early in the course of hospi-
H. influenzae seems to be declining [85]. There is evidence to talization [94]. A high carbohydrate load via parenteral ali-
suggest that more potent, broad-spectrum antibiotics such as mentation may, however, result in increased carbon dioxide
amoxicillin-clavulanate or respiratory fluoroquinolones may production [95]. In a patient with a limited ability to in-
be associated with better outcomes [86]. crease ventilation, significant worsening of arterial hypercap-
nia can result, even requiring the institution of mechanical
Corticosteroids. Short-term use of corticosteroids has been ventilatory support. Nonprotein calories in the form of fat
generally advocated in acute exacerbations, although it is only cause a lower production of carbon dioxide compared with
recently that this has been supported by randomized clinical tri- isocaloric amounts of carbohydrate, and a higher fat and re-
als (Table 49.3). A short course (2 weeks) of prednisone results duced carbohydrate supplement may lessen the degree of hy-
in a more rapid improvement in FEV1 , reduced rate of deterio- percapnia in selected patients [96]. Such a modification in
ration, and shortened hospital stay and prevents relapses [87 nutritional support is only necessary when excessive calories
90]. The optimal dose and duration are unclear, but no benefit are given [97]. A recent systematic overview in patients with
was noted with an 8-week course compared with 2 weeks [89]. COPD suggested that patients with marginal ventilatory re-
The major adverse effect is hyperglycemia. serve might benefit from a dietary regimen in which a high
percentage of calories are supplied by fat [98]. Although there
Other Interventions. In stable patients with COPD, chest per- are reports of the benefits of nutritional repletion, trials of
cussion and postural drainage produce no significant improve- more than 2 weeks failed to show consistent benefit on body
ment in airflow or gas exchange [91]. Moreover, there is no weight.

TA B L E 4 9 . 3
SUMMARY OF CLINICAL TRIALS OF CORTICOSTEROID USE IN EXACERBATIONS OF CHRONIC OBSTRUCTIVE
PULMONARY DISEASE

Patients Study design Therapeutic regimen Outcome Reference

271 Randomized controlled Methylprednisolone 125 mg every 6 h for Improved FEV1 , shorter [89]
72 h IV followed by a tapering oral course hospital stay
of prednisone (2 or 8 wk)
56 Randomized controlled 30 mg prednisolone orally for 14 d Improved FEV1 , shorter [88]
hospital stay
30a Retrospective IV in ED (mean dose 365 mg hydrocortisone) Decreased relapse rate at 48 h [90]
followed by oral (mean dose 42 mg)
96 Randomized controlled 100 mg methylprednisolone as a single dose No difference in FEV1 at 5 h or [137]
IV in ED relapse at 48 h
a
Thirty patients with 90 acute exacerbations treated with or without steroids.
ED, emergency department; FEV1 , forced expiratory volume in 1 second; IV, intravenously.
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530 Section IV: Pulmonary Problems in the Intensive Care Unit

Patients with acute respiratory failure may have elevated vival; and (i) a decrease in red blood cell mass and hematocrit
levels of antidiuretic hormone, decreased renal blood flow, and [116].
right heart failure [99]. Diuretics are helpful in correcting these A simple relation between PaO2 and oxygen delivery often
problems [99], but a complicating metabolic alkalosis may fol- does not exist in these patients. In individuals with an acute
low. In patients with COPD, digitalis preparations are of little exacerbation of COPD with severe arterial hypoxemia, the ad-
benefit in the routine treatment of cor pulmonale unless con- ministration of supplemental oxygen results in a direct increase
comitant left ventricular dysfunction is found [100]. Further- in oxygen delivery with no change in cardiac output [117]. On
more, because patients with acute decompensation of COPD the other hand, in patients with acute exacerbations of COPD
tend to be at increased risk of digitalis toxicity [101], digitalis and moderate degrees of arterial hypoxemia, the result of sup-
should be avoided in this setting. plemental oxygen is no change in oxygen delivery but a de-
Respiratory stimulants such as doxapram and nikethamide crease in previously elevated cardiac output [117].
have not been shown to be beneficial, using clinically relevant Administration of supplemental oxygen is often associated
end points [73,102], and are associated with substantial toxic- with an additional rise in the PaCO2 . This is probably due to a
ity [73]. Almitrine may increase ventilation and improve V/ Q change in dead space or shift of the hemoglobinoxygen bind-
relationships in patients with COPD [103], but there is a high ing curve rather than decreased respiratory drive [118]. This
incidence of significant side effects [104]. rise is expected and should not be specifically treated unless it is
excessive, resulting in a trend toward acute respiratory acidosis
Specific Therapy on serial ABG determinations, with CNS or cardiovascular side
effects. Should this occur, the supplemental oxygen should not
Exacerbations of COPD are usually due to upper or lower be discontinued abruptly but rather decreased slowly until the
airway infections (e.g., viral or bacterial, or both). However, PaCO2 returns to a more acceptable level [73] and the situation
should a specific condition among those listed in Table 49.1 is stabilized. Because abrupt discontinuation of supplemental
be determined to be the cause of deterioration in respiratory oxygen may not be associated with a prompt increase in ventila-
status and specific treatment exists (e.g., anticoagulation for tion, the PaCO2 may not fall. Therefore, abrupt withdrawal of
pulmonary embolism), it should be instituted. supplemental oxygen may additionally depress the already low
PaO2 , causing more profound arterial hypoxemia [73]. Carbon
dioxide narcosis may occur with excessive oxygen therapy but
Respiratory Failure is much less likely with low-flowcontrolled oxygen therapy
[73]. It occurs more commonly in patients with more marked
Administration of controlled oxygen therapy is probably the hypoxemia [79]. Clinically significant hypercapnia is less likely
single most useful treatment in COPD-induced hypercapnic to occur with oxygen therapy administered to maintain oxy-
respiratory failure. The increasing availability and evidence for gen saturation at 91% to 92% [119]. Oxygen therapy is more
the benefits of noninvasive ventilation has decreased the need effective with a prescription chart [120]
for invasive ventilation and led to improved outcomes. The de-
cision to intubate the trachea and mechanically ventilate the
lungs is often complicated by concerns that it may not be easy Mechanical Ventilation
to wean the patient from the ventilator but most individuals Whether to institute mechanical ventilatory support is often a
with an acute reversible process are successfully liberated from difficult decision in hypercapnic respiratory failure associated
the ventilator [105107]. Those with significant comorbidity with COPD. This decision reflects a continuous reassessment
and high severity of illness scores are more likely not to sur- of the patients status, including the trend of ABG values and
vive an episode of acute respiratory failure [108,109]. Patients determining whether the patient is strong and alert enough to
with progressive end-stage lung disease should be identified and clear his or her secretions and protect the airway. The pres-
carefully assessed to determine whether a reversible component ence of worsening acute respiratory acidosis with a low arte-
exists. rial pH (e.g., less than 7.2) and inadequate PaO2 (e.g., less than
55 mm Hg) or CNS and cardiovascular dysfunction dictates the
Supplemental Oxygen need for assisted ventilation. Difficulty arises when the data are
not as definitive. An alternative to endotracheal intubation is
Patients with exacerbations of COPD may present with pro- noninvasive mask ventilation, and early institution of this mode
found hypoxemia. A PaO2 below 34 mm Hg in otherwise nor- of ventilatory support is associated with a significant outcome
mal animals is associated with the development of lactic aci- benefit.
dosis [110]. Any concomitant decrease in cardiac output leads
to the development of lactic acidosis at even higher levels of
PaO2 [110]. A low PaO2 leads to pulmonary arterial vasocon- Noninvasive Ventilation. Numerous randomized trials and
striction and pulmonary hypertension [111]. Renal function, recent systematic reviews have clearly shown that the use of
particularly the excretion of a free water load, may be signifi- noninvasive ventilation (NIV) markedly improves in-hospital
cantly impaired when PaO2 falls below 40 mm Hg [112]. The outcomes in acute exacerbations of COPD [121123] (Table
mechanism appears to be CNS release of antidiuretic hormone 49.4). See Chapter 59 for a comprehensive discussion of this
in response to severe hypoxemia [113]. Other consequences topic in general and in COPD patients.
include CNS dysfunction [114] and cardiac arrhythmias or is-
chemia [115].
The use of supplemental oxygen leads to (a) a decrease in Invasive Mechanical Ventilation. Although it is prudent to
anaerobic metabolism and lactic acid production; (b) an im- avoid intubating the trachea in a patient with COPD whenever
provement in brain function; (c) a decrease in cardiac arrhyth- possible, the development of stupor or coma may necessitate
mias and ischemia; (d) a decrease in pulmonary hypertension; emergency intubation, a potentially disastrous complication.
(e) an improvement in right-sided heart function with improve- The decision to institute mechanical ventilatory support is a
ment in right-sided heart failure; (f) a decrease in the release of clinical one and supported by lack of response or intolerance
antidiuretic hormone and an increase in the kidneys ability to to NIV or progressive acidosis or respiratory rate. See Chapter
clear free water; (g) a decrease in the formation of extravascular 58 for a comprehensive discussion of this topic in general and
lung water (i.e., pulmonary edema); (h) an improvement in sur- in patients with COPD.
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Chapter 49: Respiratory Failure Part IV: Chronic Obstructive Pulmonary Disease 531

TA B L E 4 9 . 4 sion or ventilation was required. In-hospital mortality rates of


8% to 25% [124] are generally quoted with 1-year mortality
RECOMMENDATIONS BASED ON RANDOMIZED ranging from 21% to 43% [125,126]. The prognosis for pa-
CONTROLLED CLINICAL TRIALS tients treated in the ICU is significantly worse with in-hospital
mortality as high as 25% and 1-year mortality approaching
Recommendation References 39% [127,128]. Although a dismal outcome is often quoted
for patients with COPD who require prolonged ventilation
1. Give bronchodilators [4449] (more than 21 days), half of these patients can ultimately be
2. Give inhaled corticosteroids for people with [5560] weaned [107]. Systemic markers of health such as APACHE
an FEV1 less then 50%60% predicted II scores and serum albumin are the best predictors of ICU
3. Give antibiotics for purulent exacerbations of [35,8284] survival.
COPD Readmission rates following hospitalization range from
4. Use oxygen [64,65] 61% to 80% in the year following discharge. Risk factors for
5. Use noninvasive ventilation for patients with [121123] readmission include a low FEV1 , number of days in hospital in
severe exacerbations and respiratory failure the previous year, low physical activity scale, and poor overall
quality of life scores [129].
The major predictors of hospital mortality in patients with
acute exacerbations of COPD appear to be indices of nonres-
piratory organ dysfunction (e.g., serum albumin, body mass
index) and severity of illness [108], whereas the severity of
PROGNOSIS respiratory disease predicts 1-year mortality [130]. Age older
than 65 years is an important prognostic indicator [130,131].
The prognosis for patients admitted to hospital for an acute Of note, parameters of cardiac dysfunction (cor pulmonale,
exacerbation of COPD is variable and is related to the sever- arrhythmias) are important determinants of poor outcome
ity of the underlying disease and whether an ICU admis- [106,130].

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534 Section IV: Pulmonary Problems in the Intensive Care Unit

CHAPTER 50 RESPIRATORY FAILURE


PART V: EXTRAPULMONARY CAUSES OF
RESPIRATORY FAILURE
HELEN M. HOLLINGSWORTH, MELVIN R. PRATTER AND RICHARD S. IRWIN

The conditions that cause respiratory failure primarily by their the position of the alveolar and arterial points on the oxyhe-
effect on structures other than the lungs are discussed in this moglobin dissociation curve related to ventilationperfusion
chapter. Severe impairment of the extrapulmonary compart- inequalities [12]. Thus, arterial hypercapnia with a normal
ment produces respiratory failure through the mechanism of P(Aa)O2 gradient is consistent with pure extrapulmonary res-
hypoventilation (see Chapter 46), so the resultant respiratory piratory failure, but a normal P(Aa)O2 cannot, by itself, rule
failure is always hypercapnic. Extrapulmonary causes account out severe COPD.
for up to 17% of all cases of hypercapnic respiratory failure Pulmonary parenchymal disease can also exist concomi-
[1]. This chapter is organized to follow sequential sections of tantly with extrapulmonary dysfunction. For example, a pa-
pathophysiology, diagnosis, differential diagnosis, and treat- tient with polymyositis can have respiratory muscle weakness
ment. in addition to interstitial pulmonary fibrosis. This may be sug-
gested by the combination of hypercapnia and only mild-to-
moderate widening of the P(Aa)O2 gradient. A gradient be-
PATHOPHYSIOLOGY tween 20 and 30 mm Hg in the presence of arterial hypercapnia
should raise the suspicion that a significant element of extra-
The extrapulmonary compartment includes the (a) central ner- pulmonary dysfunction may be present. It is also important to
vous system (CNS), (b) peripheral nervous system, (c) respira- realize that even when the P(Aa)O2 gradient exceeds 30 mm
tory muscles, (d) chest wall, (e) pleura, and (f) upper airway Hg, some degree of extrapulmonary dysfunction can also be
[2]. Because many conditions can cause extrapulmonary respi- present in association with significant pulmonary impairment.
ratory failure, it is helpful to categorize them according to the For example, when hypercapnic respiratory failure results from
specific component affected by the disease process (Fig. 50.1). an acute exacerbation of COPD, respiratory muscle fatigue of-
We have limited the discussion that follows to descriptions of ten contributes to the development of carbon dioxide reten-
the individual diseases and conditions that are most impor- tion [13]. A less common example is the presence of a large
tant to the topic of respiratory failure. They are summarized in abdominal ventral hernia in a patient with COPD. The resul-
Tables 50.1 through 50.4. tant paradoxic breathing pattern can contribute significantly
The pathophysiology of extrapulmonary respiratory fail- to abnormal gas exchange and increased dyspnea [14].
ure is described in Chapter 45. Functionally, extrapulmonary
disorders can lead to hypercapnic respiratory failure due to
a decrease in normal force generation (e.g., CNS dysfunction,
peripheral nervous system abnormalities, or respiratory muscle Decrease in Normal Force Generation
dysfunction) or an increase in impedance to bulk flow venti-
lation (e.g., chest wall and pleural disorders or upper airway Because the inspiratory muscles generate the force that results
obstruction) [3]. in ventilation, any condition that directly or indirectly impairs
respiratory muscle function can result in decreased force gener-
ation [3]. Dysfunction of the respiratory center, peripheral ner-
vous system pathways, or the respiratory muscles themselves
DIAGNOSIS decreases the force available to produce ventilation. If this im-
pairment is severe enough, the level of minute ventilation will
General Considerations be insufficient to clear the amount of carbon dioxide produced
by ongoing metabolic processes, and hypercapnic respiratory
Arterial hypercapnia in the presence of a normal alveolar failure results.
arterial oxygen tension [P(Aa)O2 ] gradient on room air is the An acute decrease in CNS output sufficient to result in hy-
sine qua non of extrapulmonary respiratory failure [4]. The percapnic respiratory failure (e.g., acute narcotic overdose) is
normal gradient reflects the fact that in pure extrapulmonary usually accompanied by obvious evidence of generalized CNS
failure distal gas exchange is normal, and the decrease in the depression. In contrast, a chronic (e.g., primary alveolar hy-
partial pressure of arterial oxygen (PaO2 ) directly reflects the poventilation) or episodic (e.g., central sleep apnea) cause of
decrease in the partial pressure of alveolar oxygen (PAO2 ). A decreased impulse formation may present a much more dif-
P(Aa)O2 gradient of less than 20 mm Hg in the presence of ficult diagnostic dilemma. Tests to evaluate respiratory center
an elevated partial pressure of carbon dioxide (PaCO2 ) is, with drive, such as voluntary hyperventilation, carbon dioxide stim-
few exceptions, diagnostic of extrapulmonary respiratory fail- ulation, or polysomnography, may be necessary to define the
ure [511]. The main exception occurs in patients with chronic problem.
obstructive pulmonary disease (COPD) who have increasing Peripheral nervous system dysfunction or primary weakness
hypercapnia [12]. Their P(Aa)O2 gradient can occasionally of the respiratory muscles is often indicated by the presence of
narrow to normal, probably related to substantial changes in certain suggestive clinical findings that vary depending on the
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Chapter 50: Respiratory Failure Part V: Extrapulmonary Causes of Respiratory Failure 535

less than 40 cm H2 O is generally associated with a poor cough


and difficulty clearing secretions [19].
A second measurement that is valuable in predicting the de-
velopment of arterial hypercapnia due to neuromuscular weak-
ness is the vital capacity. It can be performed either in the
pulmonary function laboratory or at the bedside. [15,19]. Al-
though a vital capacity of less than 1 L, or less than 15 mL
per kg of body weight is commonly associated with arterial
hypercapnia [1,19], the vital capacity is a less sensitive pre-
dictor of arterial hypercapnia than is the maximal inspiratory
pressure, particularly in patients with chest wall disorders such
as kyphoscoliosis [16]. Significant arterial hypercapnia is un-
likely to occur with an inspiratory pressure more negative than
30 cm H2 O; however, arterial hypercapnia may be present
with a vital capacity as high as 55% or as low as 20% of the
predicted value [15,16].
The measurement of transdiaphragmatic pressures (Pdi ) and
diaphragmatic electromyograms (EMGs), although not com-
monly used clinically, may be helpful. An inspiratory effort as-
sociated with a Pdi consistently more than 40% of maximum
predictably results in diaphragmatic fatigue [20]. Therefore, it
follows that patients with diaphragmatic weakness and a re-
duced maximum Pdi are at risk for developing diaphragmatic
FIGURE 50.1. Schematic representation of the anatomy of the respi- fatigue and respiratory failure, even in the face of normal inspi-
ratory system. ratory pressure [20]. Similarly, a decrease of more than 20%
from baseline in the high- to low-frequency ratio as measured
by the diaphragmatic EMG indicates diaphragmatic fatigue
and portends the development of hypercapnic failure [21,22].
specific entity present (see following discussion). Respiratory
muscle fatigue or weakness may be suspected clinically and
documented using a number of tests designed to evaluate res- Central Nervous System Dysfunction
piratory muscle function.
Symptoms are usually nonspecific; patients may report dys- The respiratory center, located in the brainstem, is composed of
pnea on exertion, either when supine (bilateral diaphragmatic two main parts, the medullary center and the pneumotaxic cen-
paralysis) or when upright (C56 quadriplegia). Reports of ter [23,24]: The medullary center is responsible for initiation
weakness in other muscle groups, difficulty swallowing, and and maintenance of spontaneous respiration, and the pneu-
change in voice volume or tone may be other clues. Physical motaxic center in the pons helps coordinate cyclic respiration.
findings of changes in the rate, depth, and pattern of breath- A decrease in central drive can occur due to a direct central
ing suggest stressed, fatigued, or weakened respiratory mus- loss of sensitivity to changes in PaCO2 and pH or a peripheral
cles. For example, an increased respiratory rate, a decreased chemoreceptor loss of sensitivity to hypoxia as a result of CNS
tidal volume, and paradoxic inward motion of the anterior ab- depressants, metabolic abnormalities, structural lesions, pri-
dominal wall during inspiration may be observed. The latter mary alveolar hypoventilation, and central sleep apnea (Table
finding indicates a failure of the diaphragm to contract suffi- 50.1) [2543].
ciently to descend and move the abdominal contents downward
and the abdominal wall outward during inspiration. A breath-
ing pattern that cycles between predominantly chest wall or Peripheral Nervous System Dysfunction
predominantly abdominal wall motion, called respiratory al-
ternans, represents the alternating contraction of intercostal Disruption in impulse transmission from the respiratory center
and accessory muscles, on the one hand, and the diaphragm, to the respiratory muscles can eventuate in respiratory fail-
on the other. The assumption is that these two muscle groups ure. This disruption can be caused by spinal cord disease [44],
alternate in their contribution to the work of breathing, allow- anterior horn cell disease [45,46], peripheral neuropathy, or
ing one another to rest during periods of muscle overload or neuromuscular junction blockade [19] (Table 50.2) [5,25,44
fatigue. 88]. Denervation of the inspiratory muscles may occur as part
Two readily available tests can be useful diagnostically to of a generalized process (e.g., GuillainBarre syndrome, myas-
help assess respiratory muscle function. First, measurement of thenia gravis [19]) or as an isolated abnormality (e.g., phrenic
maximal inspiratory and expiratory pressures at the mouth is nerve palsy secondary to hypothermic cardioplegia during car-
easy to perform, noninvasive, and can accurately predict the de- diac surgery [67,89]).
velopment of hypercapnic respiratory failure due to decreased Peripheral nervous system dysfunction severe enough to
respiratory muscle force generation [15,16]. Arterial hypercap- produce hypercapnic respiratory failure is always associated
nia due to respiratory muscle weakness is generally not seen with pulmonary function test findings of a reduced vital ca-
until the maximal inspiratory pressure is reduced to 30% or pacity (usually less than 50% of the predicted value [15,19])
less of normal [15,16]. Although normal predicted values vary and markedly decreased maximal inspiratory and expiratory
(primarily on the basis of age and gender [17,18]), a maximal pressures (usually 30% of the predicted pressures [15,19,55]).
inspiratory pressure less negative than 30 cm H2 O is likely This type of respiratory failure is characterized by an ineffec-
to be associated with arterial hypercapnia [16,19]. Maximal tive cough and a high incidence of aspiration, atelectasis, and
expiratory pressures are also reduced when there is respiratory pneumonia [5].
muscle weakness, and in some neuromuscular disorders, the The effect on the respiratory system of interruption of CNS
decrease may be even greater than that of the corresponding impulse transmission due to spinal cord abnormalities is highly
inspiratory pressure [16]. A maximal expiratory pressure of dependent on the level of the injury [44,47]. A lesion at the C3
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536 Section IV: Pulmonary Problems in the Intensive Care Unit

TA B L E 5 0 . 1
RESPIRATORY FAILURE CAUSED BY CENTRAL NERVOUS SYSTEM DYSFUNCTION

Causes [Reference] Salient clinical features Diagnostic tests Treatment

Central nervous system Pupillary changes Toxicology screen See Section 10 (Pharmacology,
depressant drugs [2527] Needle marks Electrocardiogram in tricyclic Overdoses, and Poisonings)
overdose
Hypothyroidism [28] Myxedema Thyroid function tests Cautious thyroid replacement
Starvation [29] Cachexia Albumin Nutrition
Diarrhea Cholesterol
Metabolic alkalosis [30] Lethargy Arterial blood gases See Chapter 71
Confusion Serum electrolytes
Structural brainstem damage Localizing neurologic
[27,31,32] findings
Neoplasm Headache CT, MRI, cerebrospinal fluid Radiation, chemotherapy
cytology
Infection Headache, fever CT, MRI Antimicrobial therapy
CT, MRI, cardiac echo
Primary alveolar Daytime Blunted or absent ventilatory Nighttime ventilatory support
hypoventilation (Ondines hypersomnolence response to CO2 , O2 in Electrophrenic pacing
curse) [3341] Headache inspired gas Medroxyprogesterone acetate
Rarely dyspneic Normal pulmonary function Supplemental oxygen
Polycythemia tests
Cor pulmonale
Central sleep apnea [31,4143] Same as primary alveolar Polysomnography: apnea Nighttime ventilatory support
hypoventilation without respiratory effort Electrophrenic pacing
Normal CO2 , O2 response Supplemental oxygen
curves while awake

, decreased; increased; CT, computed tomography; MRI, magnetic resonance imaging.

vertebral level or above abolishes both diaphragmatic and in- the distal extremities, hyperreflexia, fasciculations, and bulbar
tercostal activity, leaving only some residual accessory muscle paralysis [45]. Although respiratory failure usually develops
function [47]. The result is severe hypercapnic respiratory fail- late in the course of the disease, it may rarely be the presenting
ure. Acute spinal cord lesions at the C5 and C6 levels produce manifestation [45]. Repetitive episodes of aspiration secondary
an immediate fall in the vital capacity to 30% of the predicted to bulbar dysfunction may contribute to respiratory impair-
value, due to loss of intercostal and abdominal muscle function ment [5]. It has been speculated that antecedent poliomyelitis
[44]. This is associated with a limitation of both inspiratory ca- may be involved in some cases of amyotrophic lateral sclero-
pacity and active expiration. Within approximately 3 months sis [53]. A postpolio syndrome, characterized by new, slowly
of injury, however, the denervated muscles become stiff, which progressive muscle weakness, may develop years after recovery
enables improved diaphragmatic efficiency. This improvement from acute poliomyelitis [57].
usually leads to an increase in the vital capacity to 50% to 60% Polyneuropathies with prominent motor neuron involve-
of normal. Midthoracic spinal cord lesions have relatively little ment, (e.g. GuillainBarre syndrome) can affect the respira-
impact on respiratory muscle function because they principally tory nerves and lead to respiratory failure (see Chapter 175)
affect the abdominal muscles, resulting in only a limitation of [25]. Symmetric, predominantly distal muscle weakness with
active expiration and cough [5,47]. absent tendon reflexes is the typical presentation [25]. In one
Most spinal cord diseases interrupt impulse transmission, series of patients with GuillainBarre syndrome, 28% required
resulting in respiratory muscle weakness, but two notable ex- mechanical ventilatory assistance. The average duration of me-
ceptions exist: tetanus and strychnine poisoning. In both condi- chanical ventilation was 9 weeks (range, 3 weeks to 7 months).
tions, inhibitory influences at the spinal cord and anterior horn Although the mortality rate is generally low, 21% of hospital-
cell level decrease [5152], causing a simultaneous increase in ized patients died in one series [90]. GuillainBarre syndrome
motor activity to groups of muscles that are normally antago- may be associated with autonomic dysfunction including new-
nistic to one another. This results in intense muscle spasms, in- onset hypertension (57%), sinus tachycardia (50%), postural
cluding involvement of the upper airway muscles, diaphragm, hypotension (43%), or facial flushing (25%) [90].
and intercostal muscles. The repetitive spasms and episodes of Dinoflagellate toxin poisoning, from red tide-contaminated
apnea, result in severe arterial hypoxemia, hypercapnia, and shellfish and ciguatera-contaminated reef and other fish, is a
metabolic acidosis [51,52]. dramatic but uncommon cause of peripheral neuropathy re-
Diseases that involve the anterior horn cells of the spinal sulting that can produce respiratory failure [6166]. The re-
cord interrupt efferent impulse transmission. Amyotrophic lat- sponsible agents are heat-stable neurotoxins that interfere with
eral sclerosis (ALS) is the most common anterior horn cell dis- action potential propagation along peripheral nerves. During
ease causing respiratory failure [5,45,47]. In most cases of ALS, the warm summer months, the dinoflagellates that produce the
the patient develops segmental muscular atrophy, weakness of toxins proliferate and are ingested by shellfish and fish. The
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TA B L E 5 0 . 2
RESPIRATORY FAILURE CAUSED BY PERIPHERAL NERVOUS SYSTEM DYSFUNCTION

Causes [Reference] Salient features Diagnostic tests Supportive

Spinal cord disease Above C5, diaphragm, Spinal X-ray film, CT, MRI Supportive, vital capacity tends to
[5,25,44,4750] intercostal and abdominal improve more than 3 mo in
activity abolished traumatic lesions C5 and below
Traumatic Below C5, diaphragm Phrenic nerve pacing for high
preserved, intercostal and cervical cord lesions with intact
abdominal activity phrenic nerve
abolished
Neoplasm Below T5, abdominal
activity diminished,
impaired force expiration
Hemorrhage
Syrinx
Infarct
Transverse myelitis
Tetanus [51] Intense muscle spasms Clinical setting Human antitetanus antiglobulin
Trismus Grams stain, anaerobic Wound debridement
Apnea culture of wound Penicillin, high dose
Metabolic acidosis History of inadequate Tetanus toxoid vaccination to
History of penetrating immunization prevent recurrence
wound
Strychnine [52] Intense muscle spasms Toxicology screen Supportive
Apnea Clinical picture Gastric lavage, charcoal
Metabolic acidosis
Anterior horn cell disease Segmental muscle atrophy EMG Supportive
Amyotrophic lateral Hyperreflexia
sclerosis Fasciculations
[5,45,46,53,54] Distal extremity weakness
Poliomyelitis [55,57]
Polyneuropathy [25] Viral illness, symmetric Elevated CSF protein without Prevention with vaccine
ascending distal muscle pleocytosis
weakness
GuillainBarre syndrome Ascending paralysis Demyelination by See Chapter 175
[25,5860] Areflexia electrophysiology tests
Autonomic dysfunction
Dinoflagellate poisoning Paresthesias of face, History of contaminated Supportive
progressive muscle shellfish ingestion
weakness starting 30 min
after ingestion of shellfish
Shellfish poisoning (red
tide) [6163]
Ciguatera poisoning Gastrointestinal symptoms Mouse bioassay, monoclonal Early gastric lavage, mannitol, avoid
[6466] Paresthesias, abnormal antibody to ciguatoxin caffeine
temperature differentiation
Bilateral phrenic nerve Severe orthopnea Fluoroscopy of diaphragm Diaphragmatic pacing
palsy [67,69] Abdominal paradoxic Surface EMG of diaphragm,
respiration transdiaphragmatic
pressure
CharcotMarieTooth Peripheral muscle weakness EMG Supportive
disease [70] and wasting, hereditary
pes cavus, hammertoes
Diphtheria [25] Numbness of lips, paralysis Throat culture Diphtheria antitoxin
of pharyngeal and Penicillin G or Erythromycin
laryngeal muscles
Tick paralysis [25] Tick exposure Find tick Remove tick
Age <10 y Normal sensation

(continued)
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538 Section IV: Pulmonary Problems in the Intensive Care Unit

TA B L E 5 0 . 2
CONTINUED

Causes [Reference] Salient features Diagnostic tests Supportive

Acute intermittent Acute polyneuropathy-like Urine for porphobilinogen, Hemin chloride, cimetidine
porphyria [25] GuillainBarre syndrome -aminolevulinic acid Avoid exacerbating drugs such as
Mental disturbance phenytoin, barbiturates,
Abdominal pain ethosuximide
Myasthenia gravis Muscle weakness EMG Anticholinesterase/calcium
(autoimmune and Rapid fatigability Tensilon test gluconate/thymectomy/
drug-induced) Antecedent surgery, Antibodies to acetylcholine glucocorticoids/
[25,7176] glucocorticoid, or receptors immunosuppressants
aminoglycoside See Chapter 176
Plasmapheresis
Eaton-Lambert syndrome Muscle wasting, hyporeflexia Incremental pattern on EMG Treatment of associated cancer 3,
[56,77] Associated cancer (e.g., small chest film 4-Diaminopyridine
cell of lung) Anticholinesterase
Critical illness Sepsis, multiorgan failure, Normal CSF, axonal Supportive
polyneuropathy generalized weakness, degeneration by NCS
[7881] areflexia
Persistent drug-induced Renal insufficiency Creatinine phosphokinase, Limit use of neuromuscular blocking
neuromuscular Glucocorticoids EMG, NCS, repetitive agents
blockade [78,82,83] nerve stimulation
Pseudocholinesterase Prolonged paralysis after Serum pseudocholinesterase Avoid succinylcholine
deficiency [25] succinylcholine EMG
Family history
Botulism [85,86] Wound infection, fever Grams stain and culture of Trivalent antitoxin
Ingestion of contaminated stool, wound, or suspected Wound debridement, penicillin G (or
food: nausea and vomiting food metronidazole if penicillin allergy)
Demonstrate toxin in stool, Nasogastric lavage
serum, or food by mouse
neutralization test
Organophosphates Dysphagia, diplopia, ptosis, History of exposure Atropine
[87,88] dysarthria RBC Acetyl cholinesterase Pralidoxime
Use of insecticides level Benzodiazepine
Cholinergic toxicity Atropine 1 mg challenge Cutaneous decontamination
(vomiting, diarrhea,
weakness, cramps,
sweating, ataxia, mental
status changes)
Neuralgic amyotrophy Shoulder and neck pain, Fluoroscopy of diaphragm, Analgesics, possible glucocorticoids
[68] upper extremity weakness, chest film, EMG
breathlessness, orthopnea

CSF, cerebrospinal fluid; CT, computed tomography; EMG, electromyogram; MRI, magnetic resonance imaging; NCS, nerve conduction study;
RBC, red blood cell.

clinical picture is virtually pathognomonic. Within 30 min- Bilateral diaphragmatic paralysis can also be idiopathic [94].
utes of ingesting contaminated shellfish, tingling and numbness The characteristic clinical findings of bilateral diaphragmatic
of the face, lips, and tongue develop. Paresthesias and muscle paralysis are severe orthopnea and marked abdominal para-
weakness follow, with rapid progression to limb and respira- doxic in the supine position [69,89,91,95]. Fluoroscopy during
tory muscle paralysis [62,63]. Multiple-case presentations from a sniff test is more helpful in identifying unilateral than bilat-
one source of exposure are common. eral diaphragm paralysis, as upward motion of the ribs during
Peripheral phrenic nerve palsies can contribute to or cause inspiration can make the diaphragm appear to descend. The
hypercapnic respiratory failure, particularly if they are bilat- diagnosis of diaphragmatic paralysis is usually confirmed by
eral [91]. Bilateral phrenic nerve palsies have been described transdiaphragmatic pressure measurements that reveal a min-
as an uncommon complication of hypothermia used for car- imal or absent Pdi gradient [91]. Electromyography of the di-
dioplegia during cardiac surgery (particularly when ice slush aphragm and phrenic nerve conduction velocity studies may
is used) [67], trauma [67,91], a variety of neurologic diseases also be helpful.
(e.g., poliomyelitis and GuillainBarre syndrome) [67,68,91], Several other causes of peripheral neuropathy can involve
CharcotMarieTooth disease [70], intrathoracic malignan- the efferent pathways to the respiratory muscles including
cies [92], and as a part of a paraneoplastic syndrome [93]. diphtheria, herpes zoster infection, tick paralysis, acute
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Chapter 50: Respiratory Failure Part V: Extrapulmonary Causes of Respiratory Failure 539

intermittent porphyria, beriberi, and a variety of metabolic dis- blocking agents and glucocorticoids and seems to be related
orders [25]. Respiratory failure associated with diphtheria is to the total dose of the neuromuscular blocking agent [83].
of delayed onset, usually occurring 4 to 6 weeks after the on- This has been particularly dramatic in previously healthy asth-
set of illness [25]. Tick paralysis is seen mainly in children in matic patients who became quadriparetic for days to weeks af-
whom the presence of the tick goes unnoticed for 5 to 6 days ter concomitant treatment with high-dose glucocorticoids and
[25]. In acute intermittent porphyria, respiratory involvement a neuromuscular-blocking agent [82].
may be a slowly progressive process or may cause an abrupt Neuromuscular blockade also may occur as a result of ad-
deterioration in respiratory function due to bilateral phrenic ministration of a variety of drugs [76]. Certain cardiovascu-
nerve paralysis [37]. Myasthenia gravis [19], botulism [84 lar drugs (e.g., Xylocaine, quinidine, procainamide, and pro-
86], organophosphate poisoning [25], and a variety of drugs pranolol), anticonvulsants (e.g., phenytoin and trimethadione),
can produce neuromuscular blockade that results in respiratory d-penicillamine, and a number of antibiotics (most notably
failure [76]. Although patients with myasthenia gravis typically the aminoglycosides) can prolong postoperative respiratory de-
show signs of obvious muscle weakness and rapid fatigabil- pression, unmask underlying myasthenia gravis, or cause a
ity, particularly of the cranial muscles, before the development drug-induced form of myasthenia gravis [76]. The definitive
of respiratory failure, acute respiratory failure is occasionally diagnosis of drug-induced neuromuscular blockade is usually
a presenting manifestation [25,72]. More commonly, respira- made in retrospect if the abnormality reverses after elimina-
tory failure complicates myasthenia gravis after surgical pro- tion of the offending agent. In some cases, the administration
cedures, following the institution of glucocorticoid therapy, or, of calcium gluconate has been reported to result in prompt
as a result of under- or overtreatment with anticholinesterase improvement in neuromuscular transmission [76].
medications [19]. Prolonged neuromuscular blockade is occasionally seen af-
Although the diagnosis of myasthenia gravis is suspected ter the administration of succinylcholine in individuals with
on clinical grounds and a positive response to edrophonium pseudocholinesterase deficiency [25]. In contrast to the usual
chloride (Tensilon) is supportive, the diagnosis is confirmed duration of paralysis of approximately 3 minutes, the effect in
by a typical EMG (decremental responses on repetitive nerve these individuals usually lasts 4 to 6 hours, during which time
stimulation) and an elevated serum level of antibodies to acetyl- they require mechanical ventilatory support [25].
choline receptors [71] (see Chapter 176). Part of the man- In botulism, neuromuscular blockade develops as a result of
agement of a patient with myasthenia gravis includes serial a neurotoxin produced by the bacteria Clostridium botulinum.
measurement of the, maximum inspiratory pressure and vital Most cases are caused by neurotoxin-contaminated food
capacity to assess the risk for respiratory failure [25]. A de- [8486], but occasionally botulism develops as a result of a
crease in maximum inspiratory pressure to a value less negative wound infected with C. botulinum [51] (see Chapter 88). Cer-
than 30 cm H2 O or a decrease in vital capacity to a liter or tain findings help to predict whether respiratory failure requir-
less is a warning sign of impending respiratory failure [19]. ing mechanical ventilation will develop. A vital capacity of
EatonLambert syndrome, a form of neuromuscular block- 30% or less of the predicted value is generally associated with
ade similar to myasthenia gravis, occurs in association with cer- hypercapnic failure [50]. Other clues are the presence of nau-
tain carcinomas, particularly small cell carcinoma of the lung sea, vomiting, diarrhea, dyspnea, ptosis, or extremity weakness
[55,56]. The neuromuscular blockade in most cases precedes on initial examination.
other evidence of the carcinoma, and the EMG shows an in- Organophosphates, commonly used in insecticides, in-
cremental pattern unlike that in true myasthenia. hibit the enzyme cholinesterase, resulting in accumulation of
Critical illness polyneuropathy occurs in the setting of sep- acetylcholine at neurosynaptic junctions. The symptoms of
sis and multiorgan failure in up to 30% of patients by clini- organophosphate poisoning are those of cholinergic toxic-
cal examination and up to 70% by electrophysiologic testing ity, including blurred vision, weakness, vomiting, diarrhea,
[78,81]. Profound generalized muscle weakness due to critical cramps, sweating, increased secretions, incoordination, twitch-
illness polyneuropathy is a major reason why these patients ing, ataxia, mental status changes, and, if severe enough, respi-
often require prolonged mechanical ventilatory support. Sim- ratory failure and death [87,88]. Respiratory muscle paralysis
ilar to patients with GuillainBarre Syndrome, patients with combines with respiratory center depression, excessive secre-
critical illness polyneuropathy also have areflexia, but in con- tions, and, possibly, bronchoconstriction to cause respiratory
trast, they also may have prominent sensory nerve findings failure [87,88] (see Chapter 128). Neuralgic amyotrophy, a dis-
and a normal cerebrospinal fluid examination. Electrophysio- order of the peripheral nervous system affecting the brachial
logic testing helps to distinguish critical illness polyneuropathy plexus, has recently been associated with diaphragmatic dys-
from GuillainBarre syndrome; in critical illness, polyneuropa- function and dyspnea [68]. It usually presents with acute severe
thy nerve conduction studies show axon degeneration rather shoulder pain that may extend to the neck, back, and arm.
than demyelination. Although the etiology of critical illness Motor weakness of the ipsilateral shoulder and arm usually
polyneuropathy is not known, it is predominantly a disease of develops within 1 month of the onset of pain. A sensory defect
older patients who stay in the intensive care unit for more than may be present in one fourth of patients. In one study [68],
28 days and who have elevated serum glucose and decreased 12 of 16 patients had bilateral diaphragm paralysis, and 4 of
albumin levels at the time of diagnosis. Approximately half of 16 had unilateral diaphragm paralysis. Mild nocturnal desat-
patients with sepsis, multiorgan system failure, and critical ill- uration, hypopneas, and obstructive sleep apneas (OSAs) were
ness polyneuropathy survive and the prognosis of survivors for found in some patients, but alveolar hypoventilation was not
significant improvement from the neuropathy is good [79] (see found.
Chapter 180 for additional details).
Prolonged administration (longer than 2 days) of neu-
romuscular blocking agents, such as pancuronium and ve- Respiratory Muscle Dysfunction
curonium, has been associated with two distinct patterns of
neuromuscular dysfunction [82]: (a) persistent neuromuscular A number of systemic myopathies feature prominent respi-
junction blockade in patients with renal insufficiency who ac- ratory muscle involvement, including muscular dystrophies,
cumulate the parent drug and its active metabolites, and (b) an myotonic disorders, inflammatory myopathies, periodic paral-
acute noninflammatory myopathy that becomes apparent as yses, metabolic storage diseases, endocrine myopathies, in-
neuromuscular transmission improves. The myopathy appears fectious myopathies, toxic myopathies, rhabdomyolysis, and
to be a consequence of an interaction between neuromuscular electrolyte disturbances (Table 50.3) [16,25,82,83,96126].
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TA B L E 5 0 . 3
RESPIRATORY FAILURE CAUSED BY RESPIRATORY MUSCLE DYSFUNCTION

Causes [Reference] Salient features Diagnostic tests Specific treatment

Muscle dystrophies Proximal muscle weakness Muscle biopsy Supportive


[101105] and atrophy Elevated CPK Duchenne: prednisone
Hereditary Genetic analysis
Myotonic dystrophies Myotonia, ptosis Muscle biopsy Supportive
[106109] Distal and facial muscle EMG genetic analysis Possibly mexiletine and
weakness and atrophy acetazolamide
Hereditary
Periodic paralyses Hypokalemic, hyperkalemic, Serum potassium Avoid precipitating factors
[25,109,110] or normokalemic Family history Carbonic anhydrase inhibitor
Genetic
Muscle weakness associated
with exercise, emotional
upset, cold, alcohol
Glycogen storage diseases Exercise-related muscle CPK, muscle biopsy with assay Supportive
[25,97,97,111] (Pompe cramping; slowly for acid maltase, muscle
and McArdle diseases) progressive muscle phosphorylase levels
weakness and atrophy
Dermatomyositis/ Proximal muscle weakness Elevated CPK, aldolase Glucocorticoids
polymyositis Rash in dermatomyositis EMG Immunosuppressants
[16,112114] Difficulty swallowing Muscle biopsy
Hyperthyroidism [115] Thyrotoxicosis heat TSH, TFTs Propylthiouracil,
intolerance, tachycardia, methimazole
hyperreflexia See Chapter 102
Hypothyroidism [25] Myxedema, cold intolerance TSH, TFTs Replace thyroid hormone
Hyporeflexia, bradycardia See Chapter 103
Hyperadrenocorticalism Cushingoid appearance Serum cortisol Depends on cause
[25,116] Dexamethasone suppression
test, adrenal CT scan
Rhabdomyolysis Muscle pain, swelling, CPK Supportive
secondary to colchicine myoglobulinuria
[117] or chloroquine
toxicity [25]
Infectious myositis Muscle tenderness, Serology Rest
Trichinosis [25,118] weakness, fever Muscle biopsy Glucocorticoids,
Viral [25] thiabendazole or
mebendazole
Hypophosphatemia Weakness Phosphate Replete
[99,100,119,120] Difficulty weaning See Chapter 105
Hypermagnesemia or Weakness or Mg++
hypomagnesemia Difficulty weaning
[100,121,122]
Hypokalemia [100] Weakness K+ Replete
Hypercalcemia [100,122] Lethargy, confusion Ca++ See Chapters 72, 105, and
116
Eosinophilia-myalgia l-tryptophan ingestion Eosinophilia Discontinue l-tryptophan
[123125] Muscle tenderness and Muscle biopsy Supportive
weakness, fasciitis
Fasciitis
Procainamide-induced Weakness Muscle biopsy, CPK Discontinue procainamide
myopathy [126] Respiratory failure
Acute myopathy Neuromuscular blocking EMG Supportive
secondary to agents Muscle biopsy
neuromuscular Glucocorticoids
blocking agents [82,83] Rapid onset weakness

, decreased; , increased; CPK, creatinine phosphokinase; CT, computed tomography; EMG, electromyography; TFT, thyroid function test;
TSH, thyroid-stimulating hormone.
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Chapter 50: Respiratory Failure Part V: Extrapulmonary Causes of Respiratory Failure 541

The clinical presentation generally is widespread skeletal tis obliterans organizing pneumonia, and alveolar hemorrhage
muscle weakness. Muscle weakness is the inability of a mus- [113,114].
cle to generate the normal expected level of force and should Procainamide has been reported to cause a necrotizing my-
be distinguished from muscle fatigue, which is the inability opathy with diaphragm involvement and respiratory failure
to generate the preexistent maximum force prior to putting [126]. Although antidouble-stranded DNA and antihistone
the muscle under load or stress. Fatigue is reversible with rest; antibodies were positive, antinuclear antibodies were absent,
weakness may be reversible with reconditioning or the reversal and the muscle biopsy did not reveal an inflammatory infiltrate.
or elimination of the causative factor (e.g. malnutrition, dis- Neuromuscular junction transmission was normal, suggesting
use atrophy). Respiratory muscle involvement and respiratory that this was not a drug-induced myasthenic syndrome. Slow
failure usually develop as the disease progresses. On occasion, improvement in muscle strength followed discontinuation of
however, respiratory failure may be the presenting manifesta- procainamide in this study.
tion of a generalized myopathy [97].
Myopathy-induced hypercapnic respiratory failure is al-
most invariably accompanied by a severely impaired cough
mechanism and an inability to clear respiratory tract secre- Increased Impedance to
tions [5]. Typical pulmonary function findings of respiratory
muscle weakness are a decrease in maximum inspiratory and Bulk Flow
expiratory pressures and, as the disease progresses, a decrease
in lung volumes [127]. In a number of pulmonary disorders, the development of hy-
The muscular dystrophies are inherited disorders that percapnic respiratory failure is the result of a marked increase
present with evidence of progressive proximal muscle weak- in impedance to ventilation (e.g., increased airflow resistance
ness and atrophy [25,101]. Duchenne and Becker muscular in COPD or asthma or increased elastic recoil in interstitial
dystrophies are caused by mutations in the dystrophin gene, fibrosis) that even normal respiratory muscle force generation
located on the X chromosome [102]. Duchenne dystrophy usu- cannot overcome [3]. It may be less widely appreciated that
ally presents at approximately 2 to 3 years of age and Becker increases in extrapulmonary impedance to ventilation also can
dystrophy at approximately 15 to 20 years of age. The limb- result in hypercapnic respiratory failure. These disorders can be
girdle muscular dystrophies are a more heterogeneous group of divided into those involving a decrease in chest wall or pleural
disorders that show both autosomal recessive and autosomal compliance (e.g., kyphoscoliosis or pleural fibrosis) and those
dominant inheritance and include mutations in different mem- involving an increase in airflow resistance, resulting from upper
bers of the sarcoglycan complex including motilin, dysferlin, airway obstruction (e.g., tracheal stenosis or laryngeal edema)
caveolin, and sarcoglycan. Myofibrillar myopathy is also asso- (Table 50.4) [5,42,43,128189].
ciated with mutations in the motilin gene and both of these may
eventuate in respiratory failure [103]. They frequently present
later in adulthood than do the dystrophin-related muscular dys-
trophies [104]. The myotonic dystrophies are autosomal dom- Chest Wall and Pleural Disorders
inant disorders linked to two chromosome loci: 19q13, where
a CTG repeat has been found in the intron of a serine threo- Kyphoscoliosis is a common cause of extrapulmonary respira-
nine protein kinase gene, and 3q21, where a CCTG repeat has tory failure [5]. The severity of the scoliosis (i.e., lateral curva-
been found in the intron of zinc finger protein 9 [106,107]. The ture of the spine) is usually the more important factor in the
most prominent clinical features are myotonia (i.e., sustained development of respiratory failure than is the kyphosis (i.e.,
contraction of muscles in response to direct stimulation), pto- dorsal curvature of the spine) [5]. In idiopathic kyphoscoliosis,
sis, prominent distal and facial muscle weakness, and atrophy chronic hypercapnic respiratory failure generally occurs when
[25,104,108]. the angle of curvature is 120 degrees or greater [5]. In contrast,
The periodic paralyses are genetic disorders characterized in paralytic kyphoscoliosis (e.g., as a result of poliomyelitis),
by attacks of muscle weakness in response to a variety of pre- the angle of curvature does not reliably predict either vital ca-
cipitating factors such as exercise, emotional upset, exposure pacity or hypercapnic respiratory failure [128]. This appears
to cold, and, in some cases, exposure to alcohol [25]. Patients to be due to a greater element of muscle weakness in para-
may exhibit hypokalemia, hyperkalemia, or normokalemia. In lytic kyphoscoliosis [128]. Even in idiopathic kyphoscoliosis,
some patients, the disease is unmasked when they become hy- however, the presence of markedly decreased chest wall com-
perthyroid. pliance is further complicated by inspiratory muscle weakness
Glycogen storage diseases result from defects in muscle [129] that contributes to the development of hypercapnic respi-
glycogenolysis or glycogen storage. Examples include acid mal- ratory failure [94]. In addition, a modest element of pulmonary
tase deficiency (type II) and McArdle disease (type V). Patients gas exchange abnormality is usually present [5].
exhibit exercise-induced muscle cramping and slowly progres- Patients with kyphoscoliosis usually report progressive dys-
sive muscle weakness, with or without atrophy [25,97,98,111]. pnea on exertion and exercise limitation for a period of years
On occasion, respiratory failure may be the presenting manifes- before actual arterial hypercapnia develops [5]. In patients
tation [97,111]. The diagnosis is confirmed by muscle biopsy with moderately advanced kyphoscoliosis, acute hypercapnic
and chemical assay for muscle acid maltase or phosphorylase respiratory failure may result from acute reversible complica-
levels [97,98]. tions such as pulmonary congestion, retained secretions, or pul-
Polymyositis and dermatomyositis are collagen vascular monary infection [130].
diseases that cause skeletal muscle inflammation. Proximal Massive chest wall obesity may be associated with sig-
muscle weakness is prominent and usually develops over a pe- nificant hypoventilation and the development of hypercap-
riod of weeks to months. Patients may have difficulty swal- nic respiratory failure [133]. This is termed the obesity-
lowing secondary to pharyngeal muscle involvement. Serum hypoventilation syndrome. The pathogenesis of respiratory
muscle enzyme levels are elevated. Typical EMG and mus- failure appears to be multifactorial and includes significant re-
cle biopsy findings confirm the diagnosis [112]. Respiratory duction in chest wall compliance, decreased respiratory mus-
muscle failure is an uncommon, but not rare complication cle efficiency, reduced or blunted respiratory center drive, and
of inflammatory myositis [16,112]. Patients with polymyositis impaired pulmonary gas exchange as a result of pulmonary
may also develop interstitial pulmonary fibrosis, bronchioli- congestion [133135].
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542 Section IV: Pulmonary Problems in the Intensive Care Unit

TA B L E 5 0 . 4
RESPIRATORY FAILURE CAUSED BY CHEST WALL, PLEURAL, AND UPPER AIRWAY DISEASES

Causes [Reference] Salient features Diagnostic tests Specific treatment

Chest wall and pleural disorders


Kyphoscoliosis Spinal curvature 120 degrees Spinal X-ray films Nighttime ventilatory
[5,128132] Progressive dyspnea on exertion Restriction on PFTs support
over several years
Obesity-hypoventilation Massive chest wall obesity Polysomnography Weight loss
[133135] sleep apnea CO2 response curve Nasal CPAP or BPAP
Chest wall compliance
Flail chest [136] Multiple rib fractures, paradoxic Chest film Mechanical positive-pressure
respiration pleuritic chest ventilation
pain
Fibrothorax [5,137139] Asbestos exposure, pleural Observation of chest wall Decortication
infection, pleural hemorrhage, Restriction on PFTs
uremia, collagen vascular Decreased maximum static
disease elastic recoil pressure
Thoracoplasty [5] Chest wall deformity secondary Restriction on PFTs Supportive
to resection of ribs Chest film
Ankylosing spondylitis [5] Limited chest expansion PFTs (functional residual Anti-inflammatory agents
Apical pulmonary fibrosis capacity, total lung capacity) Flexibility exercises
Limited lumbar mobility HLA-B27
Chronic lower back pain Spine and sacroiliac X-ray films
Upper airway obstruction
Acute epiglottis Fever, sore throat, stridor, Soft tissue films of neck See Chapter 67
[140143] dysphagia
Acute laryngeal edema
Angioedema/anaphylaxis Stridor in setting of Other evidence of Epinephrine parenterally
[142,144148] Hymenoptera sting, contrast angioedema/anaphylaxis; Cricothyroidotomy
media, or drug administration complement levels
Traumatic [149,150] Stridor after endotracheal History Inhaled racemic epinephrine
extubation Reintubation
Heliumoxygen mixture
Foreign body aspiration Unable to speak X-ray film helpful when foreign Heimlich maneuver
[151156] Stridor or apnea body below cords Bronchoscopy
Cricothyroidotomy
Retropharyngeal Associated with anticoagulation Soft tissue film of neck Reverse anticoagulation
hemorrhage [157] or head and neck surgery CT scan or tomography
Sore throat
Bilateral vocal cord Stridor Flowvolume loop See text
paralysis [158165] Aspiration Laryngoscopy
Laryngeal and tracheal Dyspnea Flowvolume loop Laser or surgical resection,
tumors [142,166170] Hoarseness; dysphonia Tomography radiation
Stridor Laryngotracheoscopy
Tracheal stenosis Progressive dyspnea Flowvolume loop Tracheostomy
[150,162,171173] History of endotracheal Tomography Stent, resection of stenosis
intubation
Tracheomalacia Laryngotracheoscopy Stent
[171,172]
Idiopathic obstructive Snoring Polysomnography Nasal CPAP, bilevel CPAP
sleep apnea Daytime hypersomnolence Protriptyline
[42,43,174188,132] Pulmonary hypertension Uvulopalatopharyngoplasty
Cor pulmonale Tracheostomy
Nocturnal oxygen
Weight loss
Adenotonsillar Daytime hypersomnolence Direct visualization Resection
hypertrophy [180] Obstructive sleep apnea stridor Lateral X-ray film
Obstructive goiter [189] Enlarged thyroid Tomography Suppression with exogenous
CT scan thyroid hormone
Resection

, decreased; , increased; CPAP, continuous positive airway pressure; CT, computed tomography; PFT, pulmonary function test.
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Chapter 50: Respiratory Failure Part V: Extrapulmonary Causes of Respiratory Failure 543

with a markedly elevated P(Aa)O2 gradient when calculated


Upper Airway Obstruction on room air, reflecting a severe derangement of distal gas ex-
change. Hypercapnic respiratory failure may also result from a
A variety of causes of upper airway obstruction involving the combination of pulmonary and extrapulmonary abnormalities.
extrathoracic upper airway or intrathoracic trachea can result This combined diagnosis is suggested by a P(Aa)O2 gradient
in the development of respiratory failure (Table 50.4). in the range of 25 to 30 mm Hg. If the extrapulmonary ab-
Significant upper airway obstruction should be considered normality is predominant, the gradient, although abnormal, is
in the patient who reports dyspnea in association with inspi- generally less than 25 mm Hg [5]. When primary pulmonary
ratory stridor (extrathoracic obstruction) or expiratory wheez- disease is severe enough to cause hypercapnia, the gradient is
ing (intrathoracic obstruction), particularly if other symptoms generally above 30 mm Hg.
suggest an upper airway process (e.g., dysphagia in epiglotti-
tis). Unless the patient is acutely ill, the diagnosis can usually
be confirmed by flowvolume loop analysis [190]. This tech-
nique not only demonstrates the presence of an upper airway TREATMENT
obstruction but usually also helps determine whether it is ex-
trathoracic or intrathoracic and variable or fixed [190]. Studies The treatment of extrapulmonary respiratory failure can be di-
such as soft tissue neck radiographs, laryngoscopy, and bron- vided into specific and supportive therapy. Supportive therapy
choscopy can identify the exact nature of the structural abnor- involves the use of noninvasive or invasive mechanical ventila-
mality. tory assistance (see Chapters 58 and 59), supplemental oxygen,
Upper airway obstruction from bilateral vocal cord paresis and techniques of airway hygiene (see Chapter 62). In addition,
or paralysis may result from a variety of causes. The most com- regardless of the primary cause of respiratory muscle weakness,
mon cause is trauma, particularly related to thyroid surgery malnutrition exacerbates it and nutritional replacement can in-
[161] and, occasionally, after endotracheal intubation [162]. crease respiratory muscle strength and function [191,192]. In
Other causes include tumors [142,166170]; cricoarytenoid selected circumstances, inspiratory resistive training of the res-
arthritis [160]; herpes simplex viral infection [163]; and neuro- piratory muscles and the use of theophylline as a positive res-
logic conditions, including GuillainBarre syndrome [160], ex- piratory muscle inotrope have been reported to improve respi-
trapyramidal disorders such as Parkinsons disease [164], and ratory muscle function and associated hypercapnic respiratory
myasthenia gravis [159]. Bilateral vocal cord paralysis should failure [193196]. Only specific forms of therapy are discussed
be considered when one of these conditions is present and the here and in Tables 50.1 through 50.4.
patient reports aspiration, dyspnea, or stridor [161]. Hoarse-
ness is usually absent during normal speech in bilateral ad-
ductor paralysis. The results of flowvolume loop analysis can Central Nervous System Depression
help confirm the presence of the typical extrathoracic vari-
able obstruction associated with bilateral vocal cord paralysis A description of specific treatment modalities for CNS depres-
[165]. sion is given in Table 50.1.
Obstructive sleep apnea (OSA) is increasingly recognized
as a cause of intermittent functional upper airway obstruction
[3,175,176]. Although obesity is a significant risk factor, OSA
can occur in its absence [175,176]. Episodic loss of pharyn-
Peripheral Nervous System Dysfunction
geal muscle tone caused by decreased respiratory center motor Treatment for peripheral nervous system disorders is outlined
output, usually during rapid eye movement sleep, results in in- in Table 50.2. In general, there is little in the way of specific
termittent airway obstruction [175,177]. This disturbance in therapy for established spinal cord or anterior horn cell dis-
respiratory center control also accounts for the mixed apneas ease. The use of phrenic nerve pacemakers for high-level cer-
(i.e., combination obstructive and central apneas) frequently vical cord transection may help treat the resultant respiratory
seen in these patients [175,177]. failure when nerve conduction studies have determined that the
Approximately 10% to 20% of patients with OSA have phrenic nerves are intact and functioning [4850,91]. If pacing
chronic alveolar hypoventilation with elevation in PaCO2 brings on OSA, tracheostomy or noninvasive positive airway
even while awake. These patients frequently have concomitant pressure may be necessary.
COPD or morbid obesity. Hypoxemia, whether just at night The availability and value of specific therapy for periph-
or all day, eventually causes cardiac arrhythmias, pulmonary eral neuropathy depend on the cause. In the case of acute
hypertension, and cor pulmonale [3,175,178,179]. GuillainBarre syndrome, plasmapheresis or intravenous in-
The diagnosis of OSA can be established by a sleep study fusion of pooled gamma-globulin may be helpful when ad-
(polysomnography) [174,175]. Other conditions that can cause ministered promptly for patients who reach or appear to be
or exacerbate OSA should be excluded, including adenoton- approaching the inability to walk without help or who have
sillar hypertrophy [180]; deviated nasal septum [176]; ret- substantial decrease in ventilatory capacity or bulbar insuffi-
rognathia or micrognathia [3]; macroglossia from acromegaly ciency (see Chapter 175 for more details on treating Guillain
[183]; endocrine and metabolic abnormalities such as hypothy- Barre syndrome).
roidism [67,184,185]; CNS depression from ethanol, barbitu- Patients with severe respiratory muscle weakness due
rates, and benzodiazepines [175,186]; and exogenous andro- to GuillainBarre syndrome require supportive mechanical
gen administration [187,188] (see Chapter 69). ventilatory assistance, usually for weeks to months, and oc-
casionally for longer than 1 year [59]. If cranial nerve involve-
ment is prominent, intubation for airway protection should
DIFFERENTIAL DIAGNOSIS be considered, even in the absence of overt respiratory failure.
Management is complicated by autonomic nervous system dys-
The major differential diagnosis of extrapulmonary respiratory function, which is commonly present and a leading cause of
failure is hypercapnic respiratory failure from intrinsic lung dis- death in this syndrome [90]. Abnormalities of increased or de-
eases (e.g., COPD) (Fig. 50.1). These conditions usually can be creased sympathetic and parasympathetic nervous system ac-
readily distinguished because they are almost always associated tivity, such as hypertension, hypotension, bradyarrhythmias,
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544 Section IV: Pulmonary Problems in the Intensive Care Unit

tachyarrhythmias, flushing, diaphoresis, and ileus, frequently be managed with noninvasive positive pressure ventilation (see
occur [90]. Because these events are often transient, minor Chapter 59 for details of noninvasive ventilation for acute res-
fluctuations in heart rate or blood pressure should not be piratory failure).
treated. When intervention is deemed necessary, short-acting When severe kyphoscoliosis is associated with significant
and easily titratable drugs should be used [90]. Because pa- chronic hypercapnic respiratory failure, nocturnal noninvasive
tients are at increased risk for deep venous thrombosis and positive pressure ventilation often results in marked improve-
pulmonary embolism, prophylactic anticoagulation should be ment in daytime function and gas exchange [131,197].
administered, according to guidelines for critically-ill patients
(see Chapter 52 for more details on anticoagulation in criti-
cally ill patients). Treatment of respiratory failure caused by Upper Airway Obstruction
myasthenia gravis is directed primarily at the myasthenia (see
Chapter 176). The first step in treating acute upper airway obstruction is to
Drug-induced neuromuscular blockade often improves sim- establish an adequate airway. Specific definitive therapy can
ply by discontinuing the offending agent [57]. Intravenous cal- then be used. In acute bacterial epiglottitis associated with sig-
cium gluconate may help to shorten the recovery time by revers- nificant respiratory distress, immediate steps are mandatory
ing the presynaptic component of the neuromuscular blockade to prevent development of total obstruction [140]. Chapter
[76]. If this fails and the patient improves after an edrophonium 67 provides a complete discussion of this and other treatment
chloride test, neostigmine bromide may be effective by revers- issues.
ing the postsynaptic component [52]. When myasthenia gravis Treatment of OSA is indicated when significant sleep-
is exacerbated or made manifest by a drug, therapy directed related apneas or hypopneas are noted in the setting of signs
specifically at the myasthenic symptoms may be required [76]. and symptoms such as morning headaches, daytime func-
Treatment of botulism is directed at minimizing further tional impairment, peripheral edema, cor pulmonale, and el-
binding of toxin to nerve endings while supporting the patient evated hematocrit. In general, nasal continuous or bilevel
until bound toxin dissipates [85] (see Chapter 88). Recovery positive pressure devices (continuous positive airway pres-
of ventilatory and upper airway muscle strength in type A bo- sure or bilevel continuous positive airway pressure) are
tulism occurs slowly; patients recover most of their strength effective [198200] (see Chapters 59 and 62). In OSA com-
in the first 12 weeks, but full recovery may take up to a year plicated by life-threatening arrhythmias, severe arterial hypox-
[86]. emia, or severe functional impairment [3,176], tracheostomy
may rarely be necessary [3,42,176]. Other treatment modali-
ties for OSA include weight loss [201], avoidance of alcohol
Respiratory Muscle Dysfunction and sedative drugs [175,186], mandibular and tongue reposi-
tioning appliances [202], and upper airway surgery other than
The treatment of myopathy depends on the cause (Table 50.3). tracheostomy (uvulopalatopharyngoplasty, tonsillectomy, ade-
Although the mechanism is not known, glucocorticoid ther- noidectomy, deviated septum repair), as appropriate [180,203].
apy has resulted in some improvement in muscle strength in When an identifiable cause of OSA is present (e.g., hy-
Duchenne muscular dystrophy [102,105]. Mexiletine and ac- pothyroidism), correction of the problem may be curative
etazolamide may be helpful in myotonic dystrophy [109]. [184,185].
Some patients with each of the different subtypes of periodic A summary of advances in the treatment of extrapulmonary
paralysis have responded well to acetazolamide, a carbonic an- respiratory failure is given in Table 50.5.
hydrase inhibitor that is kaliuretic [111]. Acetazolamide is of-
ten dramatically effective in preventing acute attacks of hy-
pokalemic periodic paralysis, perhaps by causing a metabolic
acidosis that, in turn, protects against the sudden decreases in TA B L E 5 0 . 5
potassium that provoke attacks. Certain patients benefit from ADVANCES IN THE TREATMENT OF
low-carbohydrate or low-sodium diets in addition to acetazo- EXTRAPULMONARY RESPIRATORY FAILURE
lamide. Inhalation of the -adrenergic agonist albuterol allevi-
ates acute attacks of weakness in some patients [111]. Disease Treatment
Polymyositis-induced muscle weakness often responds to
glucocorticoids or other immunosuppressants [112,114]. Mus- Duchenne muscular Glucocorticoids improve
cle weakness from hypothyroidism, hypophosphatemia, hypo- dystrophy pulmonary function and slow
magnesemia, or hypokalemia responds to replacement therapy disease progression [105].
[25,115,116,119,121,122]. GuillainBarre syndrome Both plasmapheresis and IVIG
The specific treatment of trichinosis is less than satisfactory are effective when started
[118]. Thiabendazole may eliminate intestinal worms, but only within 4 weeks of onset of
if initiated within 1 day of ingestion of larvae. Thiabendazole symptoms [60].
has no effect on the larvae that have reached the muscle and also Myasthenia gravis Plasmapheresis is effective in
does not appear to alter the course of established infections. short-term management of
The mainstays of treatment are bed rest, glucocorticoids, and myasthenic crisis [74].
anti-inflammatory analgesic agents. Trichinosis Thiabendazole and mebendazole
are effective in reducing
muscle weakness in trichinosis
Chest Wall and Pleural Disorders [118].
Obstructive sleep apnea Nasal continuous positive
Treatment for chest wall and pleural disorders is largely sup- airway pressure is effective in
portive (Table 50.4). If acute respiratory failure develops in the treatment of obstructive
kyphoscoliosis, reversible factors such as pulmonary conges- sleep apnea [200].
tion, infection, retained secretions, and other intercurrent ill-
nesses should be sought and treated [130]. Episodes of acute IVIG, intravenous immunoglobulin.
respiratory failure in patients with kyphoscoliosis can often
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Chapter 50: Respiratory Failure Part V: Extrapulmonary Causes of Respiratory Failure 545

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